[{"main_file_link":[{"url":"https://doi.org/10.1016/j.jbc.2024.107604","open_access":"1"}],"publisher":"Elsevier","author":[{"full_name":"Vogt, Austin","first_name":"Austin","last_name":"Vogt"},{"first_name":"Mary","last_name":"Szurgot","full_name":"Szurgot, Mary"},{"last_name":"Gardner","first_name":"Lauren","id":"f9dedd98-6d15-11f0-88a5-a7b4143fdec5","orcid":"0009-0000-5733-1546","full_name":"Gardner, Lauren"},{"full_name":"Schultz, David C.","last_name":"Schultz","first_name":"David C."},{"first_name":"Ronen","last_name":"Marmorstein","full_name":"Marmorstein, Ronen"}],"citation":{"apa":"Vogt, A., Szurgot, M., Gardner, L., Schultz, D. C., &#38; Marmorstein, R. (2024). HIRA complex deposition of histone H3.3 is driven by histone tetramerization and histone-DNA binding. <i>Journal of Biological Chemistry</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jbc.2024.107604\">https://doi.org/10.1016/j.jbc.2024.107604</a>","ieee":"A. Vogt, M. Szurgot, L. Gardner, D. C. Schultz, and R. Marmorstein, “HIRA complex deposition of histone H3.3 is driven by histone tetramerization and histone-DNA binding,” <i>Journal of Biological Chemistry</i>, vol. 300, no. 9. Elsevier, 2024.","short":"A. Vogt, M. Szurgot, L. Gardner, D.C. Schultz, R. Marmorstein, Journal of Biological Chemistry 300 (2024).","chicago":"Vogt, Austin, Mary Szurgot, Lauren Gardner, David C. Schultz, and Ronen Marmorstein. “HIRA Complex Deposition of Histone H3.3 Is Driven by Histone Tetramerization and Histone-DNA Binding.” <i>Journal of Biological Chemistry</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.jbc.2024.107604\">https://doi.org/10.1016/j.jbc.2024.107604</a>.","ama":"Vogt A, Szurgot M, Gardner L, Schultz DC, Marmorstein R. HIRA complex deposition of histone H3.3 is driven by histone tetramerization and histone-DNA binding. <i>Journal of Biological Chemistry</i>. 2024;300(9). doi:<a href=\"https://doi.org/10.1016/j.jbc.2024.107604\">10.1016/j.jbc.2024.107604</a>","ista":"Vogt A, Szurgot M, Gardner L, Schultz DC, Marmorstein R. 2024. HIRA complex deposition of histone H3.3 is driven by histone tetramerization and histone-DNA binding. Journal of Biological Chemistry. 300(9), 107604.","mla":"Vogt, Austin, et al. “HIRA Complex Deposition of Histone H3.3 Is Driven by Histone Tetramerization and Histone-DNA Binding.” <i>Journal of Biological Chemistry</i>, vol. 300, no. 9, 107604, Elsevier, 2024, doi:<a href=\"https://doi.org/10.1016/j.jbc.2024.107604\">10.1016/j.jbc.2024.107604</a>."},"day":"01","date_created":"2026-05-24T08:25:45Z","oa":1,"abstract":[{"lang":"eng","text":"The HIRA histone chaperone complex is comprised of four protein subunits: HIRA, UBN1, CABIN1, and transiently associated ASF1a. All four subunits have been demonstrated to play a role in the deposition of the histone variant H3.3 onto areas of actively transcribed euchromatin in cells. The mechanism by which these subunits function together to drive histone deposition has remained poorly understood. Here we present biochemical and biophysical data supporting a model whereby ASF1a delivers histone H3.3/H4 dimers to the HIRA complex, H3.3/H4 tetramerization drives the association of two HIRA/UBN1 complexes, and the affinity of the histones for DNA drives release of ASF1a and subsequent histone deposition. These findings have implications for understanding how other histone chaperone complexes may mediate histone deposition."}],"language":[{"iso":"eng"}],"oa_version":"Published Version","OA_place":"publisher","ddc":["572"],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"status":"public","title":"HIRA complex deposition of histone H3.3 is driven by histone tetramerization and histone-DNA binding","date_updated":"2026-06-02T14:52:50Z","volume":300,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledgement":"We would like to acknowledge Elliot Dean and Christina Freeman for technical assistance with recombinant protein expression in insect cells and members of the Marmorstein laboratory for many discussions related to this work. Schematic Figures were created with BioRender.com.","date_published":"2024-09-01T00:00:00Z","month":"09","publication":"Journal of Biological Chemistry","external_id":{"pmid":["39059488"]},"extern":"1","year":"2024","_id":"21913","issue":"9","article_number":"107604","intvolume":"       300","OA_type":"gold","publication_identifier":{"issn":["0021-9258"],"eissn":["1083-351X"]},"pmid":1,"publication_status":"published","doi":"10.1016/j.jbc.2024.107604","PlanS_conform":"1","type":"journal_article","DOAJ_listed":"1","article_type":"original","fulldoi":"https://doi.org/10.1016/j.jbc.2024.107604","has_accepted_license":"1","quality_controlled":"1","article_processing_charge":"Yes"},{"fulldoi":"https://doi.org/10.1016/j.jbc.2022.102343","article_type":"original","isi":1,"corr_author":"1","article_processing_charge":"No","file_date_updated":"2022-09-12T08:14:50Z","quality_controlled":"1","has_accepted_license":"1","pmid":1,"publication_identifier":{"eissn":["1083-351X"],"issn":["0021-9258"]},"article_number":"102343","intvolume":"       298","issue":"9","_id":"12082","type":"journal_article","doi":"10.1016/j.jbc.2022.102343","publication_status":"published","month":"09","date_published":"2022-09-01T00:00:00Z","acknowledgement":"We thank de Bono laboratory members for helpful comments on the article and the Mass Spec Facilities at IST Austria and Max Perutz Labs for invaluable discussions and comments on how to optimize mass spec analyses of worm samples. We are grateful to Ekaterina Lashmanova for designing the degron knock-in constructs and preparing the injection mixes for CRISPR/Cas9-mediated genome editing. All LC–MS/MS analyses were performed on instruments of the Vienna BioCenter Core Facilities instrument pool.\r\nThis work was supported by a Wellcome Investigator Award (grant no.: 209504/Z/17/Z ) to M.d.B. and an ISTplus Fellowship to M.A. (Marie Sklodowska-Curie agreement no.: 754411).","scopus_import":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ec_funded":1,"year":"2022","project":[{"grant_number":"209504/A/17/Z","_id":"23870BE8-32DE-11EA-91FC-C7463DDC885E","name":"Molecular mechanisms of neural circuit function"},{"call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"}],"external_id":{"pmid":["35933017"],"isi":["000884241800011"]},"publication":"Journal of Biological Chemistry","file":[{"date_created":"2022-09-12T08:14:50Z","success":1,"access_level":"open_access","checksum":"e726c7b9315230e6710e0b1f1d1677e9","file_name":"2022_JBC_Artan.pdf","content_type":"application/pdf","relation":"main_file","file_size":2101656,"date_updated":"2022-09-12T08:14:50Z","file_id":"12092","creator":"dernst"}],"language":[{"iso":"eng"}],"department":[{"_id":"MaDe"}],"abstract":[{"lang":"eng","text":"Proximity-dependent protein labeling provides a powerful in vivo strategy to characterize the interactomes of specific proteins. We previously optimized a proximity labeling protocol for Caenorhabditis elegans using the highly active biotin ligase TurboID. A significant constraint on the sensitivity of TurboID is the presence of abundant endogenously biotinylated proteins that take up bandwidth in the mass spectrometer, notably carboxylases that use biotin as a cofactor. In C. elegans, these comprise POD-2/acetyl-CoA carboxylase alpha, PCCA-1/propionyl-CoA carboxylase alpha, PYC-1/pyruvate carboxylase, and MCCC-1/methylcrotonyl-CoA carboxylase alpha. Here, we developed ways to remove these carboxylases prior to streptavidin purification and mass spectrometry by engineering their corresponding genes to add a C-terminal His10 tag. This allows us to deplete them from C. elegans lysates using immobilized metal affinity chromatography. To demonstrate the method's efficacy, we use it to expand the interactome map of the presynaptic active zone protein ELKS-1. We identify many known active zone proteins, including UNC-10/RIM, SYD-2/liprin-alpha, SAD-1/BRSK1, CLA-1/CLArinet, C16E9.2/Sentryn, as well as previously uncharacterized potentially synaptic proteins such as the ortholog of human angiomotin, F59C12.3 and the uncharacterized protein R148.3. Our approach provides a quick and inexpensive solution to a common contaminant problem in biotin-dependent proximity labeling. The approach may be applicable to other model organisms and will enable deeper and more complete analysis of interactors for proteins of interest."}],"oa":1,"date_created":"2022-09-11T22:01:55Z","day":"01","author":[{"first_name":"Murat","last_name":"Artan","orcid":"0000-0001-8945-6992","id":"C407B586-6052-11E9-B3AE-7006E6697425","full_name":"Artan, Murat"},{"first_name":"Markus","last_name":"Hartl","full_name":"Hartl, Markus"},{"last_name":"Chen","first_name":"Weiqiang","full_name":"Chen, Weiqiang"},{"full_name":"De Bono, Mario","orcid":"0000-0001-8347-0443","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","last_name":"De Bono","first_name":"Mario"}],"publisher":"Elsevier","citation":{"apa":"Artan, M., Hartl, M., Chen, W., &#38; de Bono, M. (2022). Depletion of endogenously biotinylated carboxylases enhances the sensitivity of TurboID-mediated proximity labeling in Caenorhabditis elegans. <i>Journal of Biological Chemistry</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jbc.2022.102343\">https://doi.org/10.1016/j.jbc.2022.102343</a>","ieee":"M. Artan, M. Hartl, W. Chen, and M. de Bono, “Depletion of endogenously biotinylated carboxylases enhances the sensitivity of TurboID-mediated proximity labeling in Caenorhabditis elegans,” <i>Journal of Biological Chemistry</i>, vol. 298, no. 9. Elsevier, 2022.","ama":"Artan M, Hartl M, Chen W, de Bono M. Depletion of endogenously biotinylated carboxylases enhances the sensitivity of TurboID-mediated proximity labeling in Caenorhabditis elegans. <i>Journal of Biological Chemistry</i>. 2022;298(9). doi:<a href=\"https://doi.org/10.1016/j.jbc.2022.102343\">10.1016/j.jbc.2022.102343</a>","short":"M. Artan, M. Hartl, W. Chen, M. de Bono, Journal of Biological Chemistry 298 (2022).","chicago":"Artan, Murat, Markus Hartl, Weiqiang Chen, and Mario de Bono. “Depletion of Endogenously Biotinylated Carboxylases Enhances the Sensitivity of TurboID-Mediated Proximity Labeling in Caenorhabditis Elegans.” <i>Journal of Biological Chemistry</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.jbc.2022.102343\">https://doi.org/10.1016/j.jbc.2022.102343</a>.","ista":"Artan M, Hartl M, Chen W, de Bono M. 2022. Depletion of endogenously biotinylated carboxylases enhances the sensitivity of TurboID-mediated proximity labeling in Caenorhabditis elegans. Journal of Biological Chemistry. 298(9), 102343.","mla":"Artan, Murat, et al. “Depletion of Endogenously Biotinylated Carboxylases Enhances the Sensitivity of TurboID-Mediated Proximity Labeling in Caenorhabditis Elegans.” <i>Journal of Biological Chemistry</i>, vol. 298, no. 9, 102343, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.jbc.2022.102343\">10.1016/j.jbc.2022.102343</a>."},"volume":298,"date_updated":"2025-04-14T07:44:00Z","status":"public","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"title":"Depletion of endogenously biotinylated carboxylases enhances the sensitivity of TurboID-mediated proximity labeling in Caenorhabditis elegans","acknowledged_ssus":[{"_id":"Bio"}],"ddc":["570"],"oa_version":"Published Version"},{"language":[{"iso":"eng"}],"department":[{"_id":"MaDe"},{"_id":"LifeSc"}],"abstract":[{"text":"Proximity labeling provides a powerful in vivo tool to characterize the proteome of subcellular structures and the interactome of specific proteins. The nematode Caenorhabditis elegans is one of the most intensely studied organisms in biology, offering many advantages for biochemistry. Using the highly active biotin ligase TurboID, we optimize here a proximity labeling protocol for C. elegans. An advantage of TurboID is that biotin's high affinity for streptavidin means biotin-labeled proteins can be affinity-purified under harsh denaturing conditions. By combining extensive sonication with aggressive denaturation using SDS and urea, we achieved near-complete solubilization of worm proteins. We then used this protocol to characterize the proteomes of the worm gut, muscle, skin, and nervous system. Neurons are among the smallest C. elegans cells. To probe the method's sensitivity, we expressed TurboID exclusively in the two AFD neurons and showed that the protocol could identify known and previously unknown proteins expressed selectively in AFD. The active zones of synapses are composed of a protein matrix that is difficult to solubilize and purify. To test if our protocol could solubilize active zone proteins, we knocked TurboID into the endogenous elks-1 gene, which encodes a presynaptic active zone protein. We identified many known ELKS-1-interacting active zone proteins, as well as previously uncharacterized synaptic proteins. Versatile vectors and the inherent advantages of using C. elegans, including fast growth and the ability to rapidly make and functionally test knock-ins, make proximity labeling a valuable addition to the armory of this model organism.","lang":"eng"}],"oa":1,"date_created":"2021-10-10T22:01:23Z","day":"01","author":[{"last_name":"Artan","first_name":"Murat","full_name":"Artan, Murat","orcid":"0000-0001-8945-6992","id":"C407B586-6052-11E9-B3AE-7006E6697425"},{"first_name":"Stephen","last_name":"Barratt","full_name":"Barratt, Stephen","id":"57740d2b-2a88-11ec-97cf-d9e6d1b39677"},{"full_name":"Flynn, Sean M.","first_name":"Sean M.","last_name":"Flynn"},{"full_name":"Begum, Farida","last_name":"Begum","first_name":"Farida"},{"full_name":"Skehel, Mark","first_name":"Mark","last_name":"Skehel"},{"first_name":"Armel","last_name":"Nicolas","full_name":"Nicolas, Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Mario","last_name":"De Bono","orcid":"0000-0001-8347-0443","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","full_name":"De Bono, Mario"}],"publisher":"Elsevier","citation":{"ista":"Artan M, Barratt S, Flynn SM, Begum F, Skehel M, Nicolas A, de Bono M. 2021. Interactome analysis of Caenorhabditis elegans synapses by TurboID-based proximity labeling. Journal of Biological Chemistry. 297(3), 101094.","mla":"Artan, Murat, et al. “Interactome Analysis of Caenorhabditis Elegans Synapses by TurboID-Based Proximity Labeling.” <i>Journal of Biological Chemistry</i>, vol. 297, no. 3, 101094, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/J.JBC.2021.101094\">10.1016/J.JBC.2021.101094</a>.","short":"M. Artan, S. Barratt, S.M. Flynn, F. Begum, M. Skehel, A. Nicolas, M. de Bono, Journal of Biological Chemistry 297 (2021).","chicago":"Artan, Murat, Stephen Barratt, Sean M. Flynn, Farida Begum, Mark Skehel, Armel Nicolas, and Mario de Bono. “Interactome Analysis of Caenorhabditis Elegans Synapses by TurboID-Based Proximity Labeling.” <i>Journal of Biological Chemistry</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/J.JBC.2021.101094\">https://doi.org/10.1016/J.JBC.2021.101094</a>.","ama":"Artan M, Barratt S, Flynn SM, et al. Interactome analysis of Caenorhabditis elegans synapses by TurboID-based proximity labeling. <i>Journal of Biological Chemistry</i>. 2021;297(3). doi:<a href=\"https://doi.org/10.1016/J.JBC.2021.101094\">10.1016/J.JBC.2021.101094</a>","apa":"Artan, M., Barratt, S., Flynn, S. M., Begum, F., Skehel, M., Nicolas, A., &#38; de Bono, M. (2021). Interactome analysis of Caenorhabditis elegans synapses by TurboID-based proximity labeling. <i>Journal of Biological Chemistry</i>. Elsevier. <a href=\"https://doi.org/10.1016/J.JBC.2021.101094\">https://doi.org/10.1016/J.JBC.2021.101094</a>","ieee":"M. Artan <i>et al.</i>, “Interactome analysis of Caenorhabditis elegans synapses by TurboID-based proximity labeling,” <i>Journal of Biological Chemistry</i>, vol. 297, no. 3. Elsevier, 2021."},"volume":297,"date_updated":"2025-04-14T07:43:46Z","title":"Interactome analysis of Caenorhabditis elegans synapses by TurboID-based proximity labeling","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"status":"public","ddc":["612"],"oa_version":"Published Version","date_published":"2021-09-01T00:00:00Z","month":"09","scopus_import":"1","acknowledgement":"We thank de Bono lab members for helpful comments on the manuscript, IST Austria and University of Vienna Mass Spec Facilities for invaluable discussions and comments for the optimization of mass spec analyses of worm samples. The biotin auxotropic E. coli strain MG1655bioB:kan was gift from John Cronan (University of Illinois) and was kindly sent to us by Jessica Feldman and Ariana Sanchez (Stanford University). dg398 pEntryslot2_mNeongreen::3XFLAG::stop and dg397 pEntryslot3_mNeongreen::3XFLAG::stop::unc-54 3′UTR entry vector were kindly shared by Dr Dominique Glauser (University of Fribourg). Codon-optimized mScarlet vector was a generous gift from Dr Manuel Zimmer (University of Vienna).","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ec_funded":1,"year":"2021","project":[{"call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425"}],"external_id":{"isi":["000706409200006"]},"publication":"Journal of Biological Chemistry","file":[{"checksum":"19e39d36c5b9387c6dc0e89c9ae856ab","success":1,"date_created":"2021-10-11T12:20:58Z","access_level":"open_access","file_id":"10121","creator":"cchlebak","date_updated":"2021-10-11T12:20:58Z","file_size":1680010,"content_type":"application/pdf","relation":"main_file","file_name":"2021_JBC_Artan.pdf"}],"publication_identifier":{"issn":["0021-9258"],"eissn":["1083-351X"]},"article_number":"101094","intvolume":"       297","issue":"3","_id":"10117","type":"journal_article","doi":"10.1016/J.JBC.2021.101094","publication_status":"published","fulldoi":"https://doi.org/10.1016/J.JBC.2021.101094","article_type":"original","isi":1,"article_processing_charge":"Yes","file_date_updated":"2021-10-11T12:20:58Z","quality_controlled":"1","has_accepted_license":"1"},{"doi":"10.1074/jbc.RA120.012628","type":"journal_article","publication_status":"published","publication_identifier":{"issn":["0021-9258"],"eissn":["1083-351X"]},"pmid":1,"_id":"7880","issue":"16","intvolume":"       295","article_processing_charge":"No","quality_controlled":"1","article_type":"original","fulldoi":"https://doi.org/10.1074/jbc.RA120.012628","isi":1,"status":"public","title":"Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact","date_updated":"2025-07-10T11:54:48Z","volume":295,"oa_version":"Submitted Version","oa":1,"abstract":[{"text":"Following its evoked release, dopamine (DA) signaling is rapidly terminated by presynaptic reuptake, mediated by the cocaine-sensitive DA transporter (DAT). DAT surface availability is dynamically regulated by endocytic trafficking, and direct protein kinase C (PKC) activation acutely diminishes DAT surface expression by accelerating DAT internalization. Previous cell line studies demonstrated that PKC-stimulated DAT endocytosis requires both Ack1 inactivation, which releases a DAT-specific endocytic brake, and the neuronal GTPase, Rit2, which binds DAT. However, it is unknown whether Rit2 is required for PKC-stimulated DAT endocytosis in DAergic terminals or whether there are region- and/or sex-dependent differences in PKC-stimulated DAT trafficking. Moreover, the mechanisms by which Rit2 controls PKC-stimulated DAT endocytosis are unknown. Here, we directly examined these important questions. Ex vivo studies revealed that PKC activation acutely decreased DAT surface expression selectively in ventral, but not dorsal, striatum. AAV-mediated, conditional Rit2 knockdown in DAergic neurons impacted baseline DAT surface:intracellular distribution in DAergic terminals from female ventral, but not dorsal, striatum. Further, Rit2 was required for PKC-stimulated DAT internalization in both male and female ventral striatum. FRET and surface pulldown studies in cell lines revealed that PKC activation drives DAT-Rit2 surface dissociation and that the DAT N terminus is required for both PKC-mediated DAT-Rit2 dissociation and DAT internalization. Finally, we found that Rit2 and Ack1 independently converge on DAT to facilitate PKC-stimulated DAT endocytosis. Together, our data provide greater insight into mechanisms that mediate PKC-regulated DAT internalization and reveal unexpected region-specific differences in PKC-stimulated DAT trafficking in bona fide DAergic terminals. ","lang":"eng"}],"language":[{"iso":"eng"}],"department":[{"_id":"SaSi"}],"main_file_link":[{"url":"https://escholarship.umassmed.edu/oapubs/4187","open_access":"1"}],"citation":{"apa":"Fagan, R. R., Kearney, P. J., Sweeney, C. G., Luethi, D., Schoot Uiterkamp, F. E., Schicker, K., … Melikian, H. E. (2020). Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact. <i>Journal of Biological Chemistry</i>. ASBMB Publications. <a href=\"https://doi.org/10.1074/jbc.RA120.012628\">https://doi.org/10.1074/jbc.RA120.012628</a>","ieee":"R. R. Fagan <i>et al.</i>, “Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact,” <i>Journal of Biological Chemistry</i>, vol. 295, no. 16. ASBMB Publications, pp. 5229–5244, 2020.","mla":"Fagan, Rita R., et al. “Dopamine Transporter Trafficking and Rit2 GTPase: Mechanism of Action and in Vivo Impact.” <i>Journal of Biological Chemistry</i>, vol. 295, no. 16, ASBMB Publications, 2020, pp. 5229–44, doi:<a href=\"https://doi.org/10.1074/jbc.RA120.012628\">10.1074/jbc.RA120.012628</a>.","ista":"Fagan RR, Kearney PJ, Sweeney CG, Luethi D, Schoot Uiterkamp FE, Schicker K, Alejandro BS, O’Connor LC, Sitte HH, Melikian HE. 2020. Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact. Journal of Biological Chemistry. 295(16), 5229–5244.","chicago":"Fagan, Rita R., Patrick J. Kearney, Carolyn G. Sweeney, Dino Luethi, Florianne E Schoot Uiterkamp, Klaus Schicker, Brian S. Alejandro, Lauren C. O’Connor, Harald H. Sitte, and Haley E. Melikian. “Dopamine Transporter Trafficking and Rit2 GTPase: Mechanism of Action and in Vivo Impact.” <i>Journal of Biological Chemistry</i>. ASBMB Publications, 2020. <a href=\"https://doi.org/10.1074/jbc.RA120.012628\">https://doi.org/10.1074/jbc.RA120.012628</a>.","ama":"Fagan RR, Kearney PJ, Sweeney CG, et al. Dopamine transporter trafficking and Rit2 GTPase: Mechanism of action and in vivo impact. <i>Journal of Biological Chemistry</i>. 2020;295(16):5229-5244. doi:<a href=\"https://doi.org/10.1074/jbc.RA120.012628\">10.1074/jbc.RA120.012628</a>","short":"R.R. Fagan, P.J. Kearney, C.G. Sweeney, D. Luethi, F.E. Schoot Uiterkamp, K. Schicker, B.S. Alejandro, L.C. O’Connor, H.H. Sitte, H.E. Melikian, Journal of Biological Chemistry 295 (2020) 5229–5244."},"author":[{"last_name":"Fagan","first_name":"Rita R.","full_name":"Fagan, Rita R."},{"full_name":"Kearney, Patrick J.","first_name":"Patrick J.","last_name":"Kearney"},{"full_name":"Sweeney, Carolyn G.","last_name":"Sweeney","first_name":"Carolyn G."},{"full_name":"Luethi, Dino","first_name":"Dino","last_name":"Luethi"},{"full_name":"Schoot Uiterkamp, Florianne E","id":"3526230C-F248-11E8-B48F-1D18A9856A87","first_name":"Florianne E","last_name":"Schoot Uiterkamp"},{"first_name":"Klaus","last_name":"Schicker","full_name":"Schicker, Klaus"},{"first_name":"Brian S.","last_name":"Alejandro","full_name":"Alejandro, Brian S."},{"last_name":"O'Connor","first_name":"Lauren C.","full_name":"O'Connor, Lauren C."},{"full_name":"Sitte, Harald H.","last_name":"Sitte","first_name":"Harald H."},{"full_name":"Melikian, Haley E.","last_name":"Melikian","first_name":"Haley E."}],"publisher":"ASBMB Publications","day":"17","date_created":"2020-05-24T22:00:59Z","year":"2020","publication":"Journal of Biological Chemistry","external_id":{"isi":["000530288000006"],"pmid":["32132171"]},"page":"5229-5244","scopus_import":"1","date_published":"2020-04-17T00:00:00Z","month":"04","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"article_type":"original","fulldoi":"https://doi.org/10.1074/jbc.ra118.002251","quality_controlled":"1","article_processing_charge":"No","_id":"8440","issue":"22","intvolume":"       293","publication_identifier":{"issn":["0021-9258","1083-351X"]},"publication_status":"published","doi":"10.1074/jbc.ra118.002251","type":"journal_article","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","page":"8379-8393","keyword":["Cell Biology","Biochemistry","Molecular Biology"],"date_published":"2018-06-01T00:00:00Z","month":"06","publication":"Journal of Biological Chemistry","extern":"1","year":"2018","author":[{"last_name":"Weinhäupl","first_name":"Katharina","full_name":"Weinhäupl, Katharina"},{"last_name":"Brennich","first_name":"Martha","full_name":"Brennich, Martha"},{"first_name":"Uli","last_name":"Kazmaier","full_name":"Kazmaier, Uli"},{"full_name":"Lelievre, Joel","last_name":"Lelievre","first_name":"Joel"},{"first_name":"Lluis","last_name":"Ballell","full_name":"Ballell, Lluis"},{"first_name":"Alfred","last_name":"Goldberg","full_name":"Goldberg, Alfred"},{"full_name":"Schanda, Paul","orcid":"0000-0002-9350-7606","id":"7B541462-FAF6-11E9-A490-E8DFE5697425","last_name":"Schanda","first_name":"Paul"},{"first_name":"Hugo","last_name":"Fraga","full_name":"Fraga, Hugo"}],"citation":{"mla":"Weinhäupl, Katharina, et al. “The Antibiotic Cyclomarin Blocks Arginine-Phosphate–Induced Millisecond Dynamics in the N-Terminal Domain of ClpC1 from Mycobacterium Tuberculosis.” <i>Journal of Biological Chemistry</i>, vol. 293, no. 22, American Society for Biochemistry &#38; Molecular Biology, 2018, pp. 8379–93, doi:<a href=\"https://doi.org/10.1074/jbc.ra118.002251\">10.1074/jbc.ra118.002251</a>.","ista":"Weinhäupl K, Brennich M, Kazmaier U, Lelievre J, Ballell L, Goldberg A, Schanda P, Fraga H. 2018. The antibiotic cyclomarin blocks arginine-phosphate–induced millisecond dynamics in the N-terminal domain of ClpC1 from Mycobacterium tuberculosis. Journal of Biological Chemistry. 293(22), 8379–8393.","ama":"Weinhäupl K, Brennich M, Kazmaier U, et al. The antibiotic cyclomarin blocks arginine-phosphate–induced millisecond dynamics in the N-terminal domain of ClpC1 from Mycobacterium tuberculosis. <i>Journal of Biological Chemistry</i>. 2018;293(22):8379-8393. doi:<a href=\"https://doi.org/10.1074/jbc.ra118.002251\">10.1074/jbc.ra118.002251</a>","chicago":"Weinhäupl, Katharina, Martha Brennich, Uli Kazmaier, Joel Lelievre, Lluis Ballell, Alfred Goldberg, Paul Schanda, and Hugo Fraga. “The Antibiotic Cyclomarin Blocks Arginine-Phosphate–Induced Millisecond Dynamics in the N-Terminal Domain of ClpC1 from Mycobacterium Tuberculosis.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry &#38; Molecular Biology, 2018. <a href=\"https://doi.org/10.1074/jbc.ra118.002251\">https://doi.org/10.1074/jbc.ra118.002251</a>.","short":"K. Weinhäupl, M. Brennich, U. Kazmaier, J. Lelievre, L. Ballell, A. Goldberg, P. Schanda, H. Fraga, Journal of Biological Chemistry 293 (2018) 8379–8393.","apa":"Weinhäupl, K., Brennich, M., Kazmaier, U., Lelievre, J., Ballell, L., Goldberg, A., … Fraga, H. (2018). The antibiotic cyclomarin blocks arginine-phosphate–induced millisecond dynamics in the N-terminal domain of ClpC1 from Mycobacterium tuberculosis. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry &#38; Molecular Biology. <a href=\"https://doi.org/10.1074/jbc.ra118.002251\">https://doi.org/10.1074/jbc.ra118.002251</a>","ieee":"K. Weinhäupl <i>et al.</i>, “The antibiotic cyclomarin blocks arginine-phosphate–induced millisecond dynamics in the N-terminal domain of ClpC1 from Mycobacterium tuberculosis,” <i>Journal of Biological Chemistry</i>, vol. 293, no. 22. American Society for Biochemistry &#38; Molecular Biology, pp. 8379–8393, 2018."},"publisher":"American Society for Biochemistry & Molecular Biology","day":"01","date_created":"2020-09-18T10:05:18Z","abstract":[{"text":"Mycobacterium tuberculosis can remain dormant in the host, an ability that explains the failure of many current tuberculosis treatments. Recently, the natural products cyclomarin, ecumicin, and lassomycin have been shown to efficiently kill Mycobacterium tuberculosis persisters. Their target is the N-terminal domain of the hexameric AAA+ ATPase ClpC1, which recognizes, unfolds, and translocates protein substrates, such as proteins containing phosphorylated arginine residues, to the ClpP1P2 protease for degradation. Surprisingly, these antibiotics do not inhibit ClpC1 ATPase activity, and how they cause cell death is still unclear. Here, using NMR and small-angle X-ray scattering, we demonstrate that arginine-phosphate binding to the ClpC1 N-terminal domain induces millisecond dynamics. We show that these dynamics are caused by conformational changes and do not result from unfolding or oligomerization of this domain. Cyclomarin binding to this domain specifically blocked these N-terminal dynamics. On the basis of these results, we propose a mechanism of action involving cyclomarin-induced restriction of ClpC1 dynamics, which modulates the chaperone enzymatic activity leading eventually to cell death.","lang":"eng"}],"language":[{"iso":"eng"}],"oa_version":"None","status":"public","title":"The antibiotic cyclomarin blocks arginine-phosphate–induced millisecond dynamics in the N-terminal domain of ClpC1 from Mycobacterium tuberculosis","date_updated":"2021-01-12T08:19:17Z","volume":293},{"scopus_import":"1","date_published":"2017-04-28T00:00:00Z","month":"04","page":"7258 - 7273","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","year":"2017","external_id":{"isi":["000400478300035"]},"file":[{"file_id":"6971","creator":"dernst","file_size":5647880,"date_updated":"2020-07-14T12:47:37Z","relation":"main_file","content_type":"application/pdf","file_name":"2017_JBC_Horsthemke.pdf","checksum":"d488162874326a4bb056065fa549dc4a","access_level":"open_access","date_created":"2019-10-24T15:25:42Z"}],"publication":"Journal of Biological Chemistry","abstract":[{"text":"Macrophage filopodia, finger-like membrane protrusions, were first implicated in phagocytosis more than 100 years ago, but little is still known about the involvement of these actin-dependent structures in particle clearance. Using spinning disk confocal microscopy to image filopodial dynamics in mouse resident Lifeact-EGFP macrophages, we show that filopodia, or filopodia-like structures, support pathogen clearance by multiple means. Filopodia supported the phagocytic uptake of bacterial (Escherichia coli) particles by (i) capturing along the filopodial shaft and surfing toward the cell body, the most common mode of capture; (ii) capturing via the tip followed by retraction; (iii) combinations of surfing and retraction; or (iv) sweeping actions. In addition, filopodia supported the uptake of zymosan (Saccharomyces cerevisiae) particles by (i) providing fixation, (ii) capturing at the tip and filopodia-guided actin anterograde flow with phagocytic cup formation, and (iii) the rapid growth of new protrusions. To explore the role of filopodia-inducing Cdc42, we generated myeloid-restricted Cdc42 knock-out mice. Cdc42-deficient macrophages exhibited rapid phagocytic cup kinetics, but reduced particle clearance, which could be explained by the marked rounded-up morphology of these cells. Macrophages lacking Myo10, thought to act downstream of Cdc42, had normal morphology, motility, and phagocytic cup formation, but displayed markedly reduced filopodia formation. In conclusion, live-cell imaging revealed multiple mechanisms involving macrophage filopodia in particle capture and engulfment. Cdc42 is not critical for filopodia or phagocytic cup formation, but plays a key role in driving macrophage lamellipodial spreading.","lang":"eng"}],"department":[{"_id":"MiSi"}],"language":[{"iso":"eng"}],"oa":1,"day":"28","date_created":"2018-12-11T11:47:49Z","publist_id":"7059","author":[{"last_name":"Horsthemke","first_name":"Markus","full_name":"Horsthemke, Markus"},{"last_name":"Bachg","first_name":"Anne","full_name":"Bachg, Anne"},{"last_name":"Groll","first_name":"Katharina","full_name":"Groll, Katharina"},{"full_name":"Moyzio, Sven","first_name":"Sven","last_name":"Moyzio"},{"full_name":"Müther, Barbara","first_name":"Barbara","last_name":"Müther"},{"full_name":"Hemkemeyer, Sandra","last_name":"Hemkemeyer","first_name":"Sandra"},{"last_name":"Wedlich Söldner","first_name":"Roland","full_name":"Wedlich Söldner, Roland"},{"full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt"},{"full_name":"Tacke, Sebastian","first_name":"Sebastian","last_name":"Tacke"},{"first_name":"Martin","last_name":"Bähler","full_name":"Bähler, Martin"},{"full_name":"Hanley, Peter","first_name":"Peter","last_name":"Hanley"}],"citation":{"short":"M. Horsthemke, A. Bachg, K. Groll, S. Moyzio, B. Müther, S. Hemkemeyer, R. Wedlich Söldner, M.K. Sixt, S. Tacke, M. Bähler, P. Hanley, Journal of Biological Chemistry 292 (2017) 7258–7273.","ama":"Horsthemke M, Bachg A, Groll K, et al. Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion. <i>Journal of Biological Chemistry</i>. 2017;292(17):7258-7273. doi:<a href=\"https://doi.org/10.1074/jbc.M116.766923\">10.1074/jbc.M116.766923</a>","chicago":"Horsthemke, Markus, Anne Bachg, Katharina Groll, Sven Moyzio, Barbara Müther, Sandra Hemkemeyer, Roland Wedlich Söldner, et al. “Multiple Roles of Filopodial Dynamics in Particle Capture and Phagocytosis and Phenotypes of Cdc42 and Myo10 Deletion.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology, 2017. <a href=\"https://doi.org/10.1074/jbc.M116.766923\">https://doi.org/10.1074/jbc.M116.766923</a>.","mla":"Horsthemke, Markus, et al. “Multiple Roles of Filopodial Dynamics in Particle Capture and Phagocytosis and Phenotypes of Cdc42 and Myo10 Deletion.” <i>Journal of Biological Chemistry</i>, vol. 292, no. 17, American Society for Biochemistry and Molecular Biology, 2017, pp. 7258–73, doi:<a href=\"https://doi.org/10.1074/jbc.M116.766923\">10.1074/jbc.M116.766923</a>.","ista":"Horsthemke M, Bachg A, Groll K, Moyzio S, Müther B, Hemkemeyer S, Wedlich Söldner R, Sixt MK, Tacke S, Bähler M, Hanley P. 2017. Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion. Journal of Biological Chemistry. 292(17), 7258–7273.","ieee":"M. Horsthemke <i>et al.</i>, “Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion,” <i>Journal of Biological Chemistry</i>, vol. 292, no. 17. American Society for Biochemistry and Molecular Biology, pp. 7258–7273, 2017.","apa":"Horsthemke, M., Bachg, A., Groll, K., Moyzio, S., Müther, B., Hemkemeyer, S., … Hanley, P. (2017). Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology. <a href=\"https://doi.org/10.1074/jbc.M116.766923\">https://doi.org/10.1074/jbc.M116.766923</a>"},"publisher":"American Society for Biochemistry and Molecular Biology","date_updated":"2025-09-11T07:03:17Z","volume":292,"title":"Multiple roles of filopodial dynamics in particle capture and phagocytosis and phenotypes of Cdc42 and Myo10 deletion","status":"public","ddc":["570"],"oa_version":"Published Version","article_type":"original","fulldoi":"https://doi.org/10.1074/jbc.M116.766923","isi":1,"article_processing_charge":"No","file_date_updated":"2020-07-14T12:47:37Z","has_accepted_license":"1","quality_controlled":"1","publication_identifier":{"issn":["0021-9258"]},"intvolume":"       292","_id":"668","issue":"17","type":"journal_article","doi":"10.1074/jbc.M116.766923","publication_status":"published"},{"date_updated":"2021-01-12T08:06:58Z","volume":286,"type":"journal_article","doi":"10.1074/jbc.m111.247395","status":"public","title":"The inflammation-associated protein TSG-6 cross-links hyaluronan via hyaluronan-induced TSG-6 oligomers","publication_status":"published","oa_version":"Published Version","abstract":[{"lang":"eng","text":"Tumor necrosis factor-stimulated gene-6 (TSG-6) is a hyalu-ronan (HA)-binding protein that plays important roles ininflammation and ovulation. TSG-6-mediated cross-linking ofHA has been proposed as a functional mechanism (e.g.for regu-lating leukocyte adhesion), but direct evidence for cross-linkingis lacking, and we know very little about its impact on HA ultra-structure. Here we used films of polymeric and oligomeric HAchains, end-grafted to a solid support, and a combination ofsurface-sensitive biophysical techniques to quantify the bindingof TSG-6 into HA films and to correlate binding to morpholog-ical changes. We find that full-length TSG-6 binds with pro-nounced positive cooperativity and demonstrate that it cancross-link HA at physiologically relevant concentrations. Ourdata indicate that cooperative binding of full-length TSG-6arises from HA-induced protein oligomerization and that theTSG-6 oligomers act as cross-linkers. In contrast, the HA-bind-ing domain of TSG-6 (the Link module) alone binds withoutpositive cooperativity and weaker than the full-length protein.Both the Link module and full-length TSG-6 condensed andrigidified HA films, and the degree of condensation scaled withthe affinity between the TSG-6 constructs and HA. We proposethat condensation is the result of protein-mediated HA cross-linking. Our findings firmly establish that TSG-6 is a potent HAcross-linking agent and might hence have important implica-tions for the mechanistic understanding of the biological func-tion of TSG-6 (e.g.in inflammation)."}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["0021-9258","1083-351X"]},"oa":1,"day":"22","intvolume":"       286","date_created":"2019-04-11T20:57:43Z","_id":"6298","main_file_link":[{"open_access":"1","url":"http://www.jbc.org/content/286/29/25675.full.pdf"}],"issue":"29","author":[{"id":"38661662-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3086-9124","full_name":"Baranova, Natalia","last_name":"Baranova","first_name":"Natalia"},{"first_name":"Erik","last_name":"Nilebäck","full_name":"Nilebäck, Erik"},{"full_name":"Haller, F. Michael","first_name":"F. Michael","last_name":"Haller"},{"full_name":"Briggs, David C.","last_name":"Briggs","first_name":"David C."},{"full_name":"Svedhem, Sofia","first_name":"Sofia","last_name":"Svedhem"},{"full_name":"Day, Anthony J.","last_name":"Day","first_name":"Anthony J."},{"first_name":"Ralf P.","last_name":"Richter","full_name":"Richter, Ralf P."}],"citation":{"apa":"Baranova, N. S., Nilebäck, E., Haller, F. M., Briggs, D. C., Svedhem, S., Day, A. J., &#38; Richter, R. P. (2011). The inflammation-associated protein TSG-6 cross-links hyaluronan via hyaluronan-induced TSG-6 oligomers. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry &#38; Molecular Biology. <a href=\"https://doi.org/10.1074/jbc.m111.247395\">https://doi.org/10.1074/jbc.m111.247395</a>","ieee":"N. S. Baranova <i>et al.</i>, “The inflammation-associated protein TSG-6 cross-links hyaluronan via hyaluronan-induced TSG-6 oligomers,” <i>Journal of Biological Chemistry</i>, vol. 286, no. 29. American Society for Biochemistry &#38; Molecular Biology, pp. 25675–25686, 2011.","short":"N.S. Baranova, E. Nilebäck, F.M. Haller, D.C. Briggs, S. Svedhem, A.J. Day, R.P. Richter, Journal of Biological Chemistry 286 (2011) 25675–25686.","chicago":"Baranova, Natalia S., Erik Nilebäck, F. Michael Haller, David C. Briggs, Sofia Svedhem, Anthony J. Day, and Ralf P. Richter. “The Inflammation-Associated Protein TSG-6 Cross-Links Hyaluronan via Hyaluronan-Induced TSG-6 Oligomers.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry &#38; Molecular Biology, 2011. <a href=\"https://doi.org/10.1074/jbc.m111.247395\">https://doi.org/10.1074/jbc.m111.247395</a>.","ama":"Baranova NS, Nilebäck E, Haller FM, et al. The inflammation-associated protein TSG-6 cross-links hyaluronan via hyaluronan-induced TSG-6 oligomers. <i>Journal of Biological Chemistry</i>. 2011;286(29):25675-25686. doi:<a href=\"https://doi.org/10.1074/jbc.m111.247395\">10.1074/jbc.m111.247395</a>","ista":"Baranova NS, Nilebäck E, Haller FM, Briggs DC, Svedhem S, Day AJ, Richter RP. 2011. The inflammation-associated protein TSG-6 cross-links hyaluronan via hyaluronan-induced TSG-6 oligomers. Journal of Biological Chemistry. 286(29), 25675–25686.","mla":"Baranova, Natalia S., et al. “The Inflammation-Associated Protein TSG-6 Cross-Links Hyaluronan via Hyaluronan-Induced TSG-6 Oligomers.” <i>Journal of Biological Chemistry</i>, vol. 286, no. 29, American Society for Biochemistry &#38; Molecular Biology, 2011, pp. 25675–86, doi:<a href=\"https://doi.org/10.1074/jbc.m111.247395\">10.1074/jbc.m111.247395</a>."},"publisher":"American Society for Biochemistry & Molecular Biology","extern":"1","year":"2011","publication":"Journal of Biological Chemistry","quality_controlled":"1","date_published":"2011-07-22T00:00:00Z","month":"07","page":"25675-25686","fulldoi":"https://doi.org/10.1074/jbc.m111.247395","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"publisher":"American Society for Biochemistry & Molecular Biology","author":[{"first_name":"Alessandra","last_name":"Corazza","full_name":"Corazza, Alessandra"},{"full_name":"Rennella, Enrico","last_name":"Rennella","first_name":"Enrico"},{"id":"7B541462-FAF6-11E9-A490-E8DFE5697425","orcid":"0000-0002-9350-7606","full_name":"Schanda, Paul","first_name":"Paul","last_name":"Schanda"},{"full_name":"Mimmi, Maria Chiara","first_name":"Maria Chiara","last_name":"Mimmi"},{"last_name":"Cutuil","first_name":"Thomas","full_name":"Cutuil, Thomas"},{"last_name":"Raimondi","first_name":"Sara","full_name":"Raimondi, Sara"},{"full_name":"Giorgetti, Sofia","first_name":"Sofia","last_name":"Giorgetti"},{"first_name":"Federico","last_name":"Fogolari","full_name":"Fogolari, Federico"},{"full_name":"Viglino, Paolo","first_name":"Paolo","last_name":"Viglino"},{"first_name":"Lucio","last_name":"Frydman","full_name":"Frydman, Lucio"},{"last_name":"Gal","first_name":"Maayan","full_name":"Gal, Maayan"},{"last_name":"Bellotti","first_name":"Vittorio","full_name":"Bellotti, Vittorio"},{"last_name":"Brutscher","first_name":"Bernhard","full_name":"Brutscher, Bernhard"},{"full_name":"Esposito, Gennaro","last_name":"Esposito","first_name":"Gennaro"}],"citation":{"ista":"Corazza A, Rennella E, Schanda P, Mimmi MC, Cutuil T, Raimondi S, Giorgetti S, Fogolari F, Viglino P, Frydman L, Gal M, Bellotti V, Brutscher B, Esposito G. 2010. Native-unlike long-lived intermediates along the folding pathway of the amyloidogenic protein β2-Microglobulin revealed by real-time two-dimensional NMR. Journal of Biological Chemistry. 285(8), 5827–5835.","mla":"Corazza, Alessandra, et al. “Native-Unlike Long-Lived Intermediates along the Folding Pathway of the Amyloidogenic Protein Β2-Microglobulin Revealed by Real-Time Two-Dimensional NMR.” <i>Journal of Biological Chemistry</i>, vol. 285, no. 8, American Society for Biochemistry &#38; Molecular Biology, 2010, pp. 5827–35, doi:<a href=\"https://doi.org/10.1074/jbc.m109.061168\">10.1074/jbc.m109.061168</a>.","short":"A. Corazza, E. Rennella, P. Schanda, M.C. Mimmi, T. Cutuil, S. Raimondi, S. Giorgetti, F. Fogolari, P. Viglino, L. Frydman, M. Gal, V. Bellotti, B. Brutscher, G. Esposito, Journal of Biological Chemistry 285 (2010) 5827–5835.","chicago":"Corazza, Alessandra, Enrico Rennella, Paul Schanda, Maria Chiara Mimmi, Thomas Cutuil, Sara Raimondi, Sofia Giorgetti, et al. “Native-Unlike Long-Lived Intermediates along the Folding Pathway of the Amyloidogenic Protein Β2-Microglobulin Revealed by Real-Time Two-Dimensional NMR.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry &#38; Molecular Biology, 2010. <a href=\"https://doi.org/10.1074/jbc.m109.061168\">https://doi.org/10.1074/jbc.m109.061168</a>.","ama":"Corazza A, Rennella E, Schanda P, et al. Native-unlike long-lived intermediates along the folding pathway of the amyloidogenic protein β2-Microglobulin revealed by real-time two-dimensional NMR. <i>Journal of Biological Chemistry</i>. 2010;285(8):5827-5835. doi:<a href=\"https://doi.org/10.1074/jbc.m109.061168\">10.1074/jbc.m109.061168</a>","ieee":"A. Corazza <i>et al.</i>, “Native-unlike long-lived intermediates along the folding pathway of the amyloidogenic protein β2-Microglobulin revealed by real-time two-dimensional NMR,” <i>Journal of Biological Chemistry</i>, vol. 285, no. 8. American Society for Biochemistry &#38; Molecular Biology, pp. 5827–5835, 2010.","apa":"Corazza, A., Rennella, E., Schanda, P., Mimmi, M. C., Cutuil, T., Raimondi, S., … Esposito, G. (2010). Native-unlike long-lived intermediates along the folding pathway of the amyloidogenic protein β2-Microglobulin revealed by real-time two-dimensional NMR. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry &#38; Molecular Biology. <a href=\"https://doi.org/10.1074/jbc.m109.061168\">https://doi.org/10.1074/jbc.m109.061168</a>"},"date_created":"2020-09-18T10:11:23Z","day":"19","language":[{"iso":"eng"}],"abstract":[{"text":"β2-microglobulin (β2m), the light chain of class I major histocompatibility complex, is responsible for the dialysis-related amyloidosis and, in patients undergoing long term dialysis, the full-length and chemically unmodified β2m converts into amyloid fibrils. The protein, belonging to the immunoglobulin superfamily, in common to other members of this family, experiences during its folding a long-lived intermediate associated to the trans-to-cis isomerization of Pro-32 that has been addressed as the precursor of the amyloid fibril formation. In this respect, previous studies on the W60G β2m mutant, showing that the lack of Trp-60 prevents fibril formation in mild aggregating condition, prompted us to reinvestigate the refolding kinetics of wild type and W60G β2m at atomic resolution by real-time NMR. The analysis, conducted at ambient temperature by the band selective flip angle short transient real-time two-dimensional NMR techniques and probing the β2m states every 15 s, revealed a more complex folding energy landscape than previously reported for wild type β2m, involving more than a single intermediate species, and shedding new light into the fibrillogenic pathway. Moreover, a significant difference in the kinetic scheme previously characterized by optical spectroscopic methods was discovered for the W60G β2m mutant.","lang":"eng"}],"oa_version":"None","title":"Native-unlike long-lived intermediates along the folding pathway of the amyloidogenic protein β2-Microglobulin revealed by real-time two-dimensional NMR","status":"public","volume":285,"date_updated":"2021-01-12T08:19:31Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","page":"5827-5835","date_published":"2010-02-19T00:00:00Z","month":"02","keyword":["Cell Biology","Biochemistry","Molecular Biology"],"publication":"Journal of Biological Chemistry","year":"2010","extern":"1","issue":"8","_id":"8473","intvolume":"       285","publication_identifier":{"issn":["0021-9258","1083-351X"]},"publication_status":"published","doi":"10.1074/jbc.m109.061168","type":"journal_article","fulldoi":"https://doi.org/10.1074/jbc.m109.061168","article_type":"original","quality_controlled":"1","article_processing_charge":"No"},{"language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"The human norepinephrine (NE) transporter (hNET) attenuates neuronal signaling by rapid NE clearance from the synaptic cleft, and NET is a target for cocaine and amphetamines as well as therapeutics for depression, obsessive-compulsive disorder, and post-traumatic stress disorder. In spite of its central importance in the nervous system, little is known about how NET substrates, such as NE, 1-methyl-4-tetrahydropyridinium (MPP+), or amphetamine, interact with NET at the molecular level. Nor do we understand the mechanisms behind the transport rate. Previously we introduced a fluorescent substrate similar to MPP+, which allowed separate and simultaneous binding and transport measurement (Schwartz, J. W., Blakely, R. D., and DeFelice, L. J. (2003) J. Biol. Chem. 278, 9768-9777). Here we use this substrate, 4-(4-(dimethylamino)styrl)-N-methyl-pyridinium (ASP+), in combination with green fluorescent protein-tagged hNETs to measure substrate-transporter stoichiometry and substrate binding kinetics. Calibrated confocal microscopy and fluorescence correlation spectroscopy reveal that hNETs, which are homo-multimers, bind one substrate molecule per transporter subunit. Substrate residence at the transporter, obtained from rapid on-off kinetics revealed in fluorescence correlation spectroscopy, is 526 μs. Substrate residence obtained by infinite dilution is 1000 times slower. This novel examination of substrate-transporter kinetics indicates that a single ASP + molecule binds and unbinds thousands of times before being transported or ultimately dissociated from hNET. Calibrated fluorescent images combined with mass spectroscopy give a transport rate of 0.06 ASP +/hNET-protein/s, thus 36,000 on-off binding events (and 36 actual departures) occur for one transport event. Therefore binding has a low probability of resulting in transport. We interpret these data to mean that inefficient binding could contribute to slow transport rates."}],"publisher":"American Society for Biochemistry and Molecular Biology","author":[{"full_name":"Schwartz, Joel","last_name":"Schwartz","first_name":"Joel"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia"},{"last_name":"Piston","first_name":"David","full_name":"Piston, David"},{"full_name":"Defelice, Louis","first_name":"Louis","last_name":"Defelice"}],"citation":{"apa":"Schwartz, J., Novarino, G., Piston, D., &#38; Defelice, L. (2005). Substrate binding stoichiometry and kinetics of the norepinephrine transporter. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology. <a href=\"https://doi.org/10.1074/jbc.M412923200\">https://doi.org/10.1074/jbc.M412923200</a>","ieee":"J. Schwartz, G. Novarino, D. Piston, and L. Defelice, “Substrate binding stoichiometry and kinetics of the norepinephrine transporter,” <i>Journal of Biological Chemistry</i>, vol. 280, no. 19. American Society for Biochemistry and Molecular Biology, pp. 19177–19184, 2005.","chicago":"Schwartz, Joel, Gaia Novarino, David Piston, and Louis Defelice. “Substrate Binding Stoichiometry and Kinetics of the Norepinephrine Transporter.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology, 2005. <a href=\"https://doi.org/10.1074/jbc.M412923200\">https://doi.org/10.1074/jbc.M412923200</a>.","ama":"Schwartz J, Novarino G, Piston D, Defelice L. Substrate binding stoichiometry and kinetics of the norepinephrine transporter. <i>Journal of Biological Chemistry</i>. 2005;280(19):19177-19184. doi:<a href=\"https://doi.org/10.1074/jbc.M412923200\">10.1074/jbc.M412923200</a>","short":"J. Schwartz, G. Novarino, D. Piston, L. Defelice, Journal of Biological Chemistry 280 (2005) 19177–19184.","ista":"Schwartz J, Novarino G, Piston D, Defelice L. 2005. Substrate binding stoichiometry and kinetics of the norepinephrine transporter. Journal of Biological Chemistry. 280(19), 19177–19184.","mla":"Schwartz, Joel, et al. “Substrate Binding Stoichiometry and Kinetics of the Norepinephrine Transporter.” <i>Journal of Biological Chemistry</i>, vol. 280, no. 19, American Society for Biochemistry and Molecular Biology, 2005, pp. 19177–84, doi:<a href=\"https://doi.org/10.1074/jbc.M412923200\">10.1074/jbc.M412923200</a>."},"date_created":"2018-12-11T11:56:54Z","publist_id":"4619","day":"13","title":"Substrate binding stoichiometry and kinetics of the norepinephrine transporter","status":"public","date_updated":"2026-08-07T09:25:18Z","volume":280,"oa_version":"None","page":"19177 - 19184","month":"05","date_published":"2005-05-13T00:00:00Z","user_id":"317138e5-6ab7-11ef-aa6d-ffef3953e345","year":"2005","extern":"1","publication":"Journal of Biological Chemistry","external_id":{"pmid":["15757904"]},"publication_identifier":{"eissn":["1083-351X"],"issn":["0021-9258"]},"pmid":1,"issue":"19","_id":"2307","OA_type":"closed access","intvolume":"       280","doi":"10.1074/jbc.M412923200","type":"journal_article","publication_status":"published","fulldoi":"https://doi.org/10.1074/jbc.M412923200","article_type":"original","article_processing_charge":"No"},{"extern":"1","year":"2003","publication":"Journal of Biological Chemistry","external_id":{"pmid":["12692128 "]},"page":"23955 - 23962","scopus_import":"1","date_published":"2003-07-27T00:00:00Z","month":"07","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"status":"public","title":"Co-expression of metabotropic glutamate receptor 7 and N-type Ca2+ channels in single cerebrocortical nerve terminals of adult rats","date_updated":"2026-05-22T10:29:51Z","volume":278,"oa_version":"Published Version","OA_place":"publisher","oa":1,"abstract":[{"text":"The modulation of calcium channels by metabotropic glutamate receptors (mGluRs) is a key event in the fine-tuning of neurotransmitter release. Here we report that, in cerebrocortical nerve terminals of adult rats, the inhibition of glutamate release is mediated by mGluR7. In this preparation, the major component of glutamate release is supported by P/Q-type Ca2+ channels (72.7%). However, mGluR7 selectively reduced the release component that is associated with N-type Ca2+ channels (29.9%). Inhibition of P/Q channels by mGluR7 is not masked by the higher efficiency of these channels in driving glutamate release when compared with N-type channels. Thus, activation of mGluR7 failed to reduce the release associated with P/Q channels when the extracellular calcium concentration, ([Ca2+]o), was reduced from 1.3 to 0.5 mM. Through Ca2+ imaging, we show that Ca2+ channels are distributed in a heterogeneous manner in individual nerve terminals. Indeed, in this preparation, nerve terminals were observed that contain N-type (31.1%; conotoxin GVIA-sensitive) or P/Q-type (64.3%; agatoxin IVA-sensitive) channels or that were insensitive to these two toxins (4.6%). Interestingly, the great majority of the responses to L-AP4 (95.4%) were observed in nerve terminals containing N-type channels. This specific co-localization of mGluR7 and N-type Ca2+-channels could explain the failure of the receptor to inhibit the P/Q channel-associated release component and also reveal the existence of specific targeting mechanisms to localize the two proteins in the same nerve terminal subset.","lang":"eng"}],"language":[{"iso":"eng"}],"main_file_link":[{"url":"https://doi.org/10.1074/jbc.M211471200","open_access":"1"}],"author":[{"full_name":"Millán, Carmelo","last_name":"Millán","first_name":"Carmelo"},{"full_name":"Castro, Enrique","first_name":"Enrique","last_name":"Castro"},{"full_name":"Torres, Magdalena","last_name":"Torres","first_name":"Magdalena"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","full_name":"Shigemoto, Ryuichi","first_name":"Ryuichi","last_name":"Shigemoto"},{"full_name":"Sánchez Prieto, José","last_name":"Sánchez Prieto","first_name":"José"}],"publisher":"Elsevier","citation":{"apa":"Millán, C., Castro, E., Torres, M., Shigemoto, R., &#38; Sánchez Prieto, J. (2003). Co-expression of metabotropic glutamate receptor 7 and N-type Ca2+ channels in single cerebrocortical nerve terminals of adult rats. <i>Journal of Biological Chemistry</i>. Elsevier. <a href=\"https://doi.org/10.1074/jbc.M211471200\">https://doi.org/10.1074/jbc.M211471200</a>","ieee":"C. Millán, E. Castro, M. Torres, R. Shigemoto, and J. Sánchez Prieto, “Co-expression of metabotropic glutamate receptor 7 and N-type Ca2+ channels in single cerebrocortical nerve terminals of adult rats,” <i>Journal of Biological Chemistry</i>, vol. 278, no. 26. Elsevier, pp. 23955–23962, 2003.","mla":"Millán, Carmelo, et al. “Co-Expression of Metabotropic Glutamate Receptor 7 and N-Type Ca2+ Channels in Single Cerebrocortical Nerve Terminals of Adult Rats.” <i>Journal of Biological Chemistry</i>, vol. 278, no. 26, Elsevier, 2003, pp. 23955–62, doi:<a href=\"https://doi.org/10.1074/jbc.M211471200\">10.1074/jbc.M211471200</a>.","ista":"Millán C, Castro E, Torres M, Shigemoto R, Sánchez Prieto J. 2003. Co-expression of metabotropic glutamate receptor 7 and N-type Ca2+ channels in single cerebrocortical nerve terminals of adult rats. Journal of Biological Chemistry. 278(26), 23955–23962.","chicago":"Millán, Carmelo, Enrique Castro, Magdalena Torres, Ryuichi Shigemoto, and José Sánchez Prieto. “Co-Expression of Metabotropic Glutamate Receptor 7 and N-Type Ca2+ Channels in Single Cerebrocortical Nerve Terminals of Adult Rats.” <i>Journal of Biological Chemistry</i>. Elsevier, 2003. <a href=\"https://doi.org/10.1074/jbc.M211471200\">https://doi.org/10.1074/jbc.M211471200</a>.","short":"C. Millán, E. Castro, M. Torres, R. Shigemoto, J. Sánchez Prieto, Journal of Biological Chemistry 278 (2003) 23955–23962.","ama":"Millán C, Castro E, Torres M, Shigemoto R, Sánchez Prieto J. Co-expression of metabotropic glutamate receptor 7 and N-type Ca2+ channels in single cerebrocortical nerve terminals of adult rats. <i>Journal of Biological Chemistry</i>. 2003;278(26):23955-23962. doi:<a href=\"https://doi.org/10.1074/jbc.M211471200\">10.1074/jbc.M211471200</a>"},"day":"27","publist_id":"4265","date_created":"2018-12-11T11:58:47Z","article_processing_charge":"No","quality_controlled":"1","article_type":"original","fulldoi":"https://doi.org/10.1074/jbc.M211471200","DOAJ_listed":"1","doi":"10.1074/jbc.M211471200","type":"journal_article","publication_status":"published","publication_identifier":{"eissn":["1083-351X"],"issn":["0021-9258"]},"pmid":1,"_id":"2633","issue":"26","intvolume":"       278","OA_type":"gold"},{"date_published":"2003-10-31T00:00:00Z","month":"10","scopus_import":"1","acknowledgement":"his work was supported by the Medical Research Council.","page":"43114 - 43120","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","year":"2003","extern":"1","external_id":{"pmid":["12923180"]},"publication":"Journal of Biological Chemistry","language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"The molecular organization of bacterial NADH: ubiquinone oxidoreductase (complex I or NDH-1) is not established, apart from a rough separation into dehydrogenase, connecting and membrane domains. In this work, complex I was purified from Escherichia coli and fragmented by replacing dodecylmaltoside with other detergents. Exchange into decyl maltoside led to the removal of the hydrophobic subunit NuoL from the otherwise intact complex. Diheptanoyl phosphocholine led to the loss of NuoL and NuoM subunits, whereas other subunits remained in the complex. The presence of N,N-dimethyldodecylamine N-oxide or Triton X-100 led to further disruption of the membrane domain into fragments containing NuoL/M/N, NuoA/K/N, and NuoH/J subunits. Among the hydrophilic subunits, NuoCD was most readily dissociated from the complex, whereas NuoB was partially dissociated from the peripheral arm assembly in N,N-dimethyldodecylamine N-oxide. A model of subunit arrangement in bacterial complex I based on these data is proposed. Subunits NuoL and NuoM, which are homologous to antiporters and are implicated in proton pumping, are located at the distal end of the membrane arm, spatially separated from the redox centers of the peripheral arm. This is consistent with proposals that the mechanism of proton pumping by complex I is likely to involve long range conformational changes."}],"oa":1,"publist_id":"5124","date_created":"2018-12-11T11:54:55Z","day":"31","publisher":"American Society for Biochemistry and Molecular Biology","citation":{"ista":"Holt P, Morgan D, Sazanov LA. 2003. The location of NuoL and NuoM subunits in the membrane domain of the Escherichia coli Complex I: implications for the mechanism of proton pumping. Journal of Biological Chemistry. 278(44), 43114–43120.","mla":"Holt, Peter, et al. “The Location of NuoL and NuoM Subunits in the Membrane Domain of the Escherichia Coli Complex I: Implications for the Mechanism of Proton Pumping.” <i>Journal of Biological Chemistry</i>, vol. 278, no. 44, American Society for Biochemistry and Molecular Biology, 2003, pp. 43114–20, doi:<a href=\"https://doi.org/10.1074/jbc.M308247200\">10.1074/jbc.M308247200</a>.","ama":"Holt P, Morgan D, Sazanov LA. The location of NuoL and NuoM subunits in the membrane domain of the Escherichia coli Complex I: implications for the mechanism of proton pumping. <i>Journal of Biological Chemistry</i>. 2003;278(44):43114-43120. doi:<a href=\"https://doi.org/10.1074/jbc.M308247200\">10.1074/jbc.M308247200</a>","short":"P. Holt, D. Morgan, L.A. Sazanov, Journal of Biological Chemistry 278 (2003) 43114–43120.","chicago":"Holt, Peter, David Morgan, and Leonid A Sazanov. “The Location of NuoL and NuoM Subunits in the Membrane Domain of the Escherichia Coli Complex I: Implications for the Mechanism of Proton Pumping.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology, 2003. <a href=\"https://doi.org/10.1074/jbc.M308247200\">https://doi.org/10.1074/jbc.M308247200</a>.","ieee":"P. Holt, D. Morgan, and L. A. Sazanov, “The location of NuoL and NuoM subunits in the membrane domain of the Escherichia coli Complex I: implications for the mechanism of proton pumping,” <i>Journal of Biological Chemistry</i>, vol. 278, no. 44. American Society for Biochemistry and Molecular Biology, pp. 43114–43120, 2003.","apa":"Holt, P., Morgan, D., &#38; Sazanov, L. A. (2003). The location of NuoL and NuoM subunits in the membrane domain of the Escherichia coli Complex I: implications for the mechanism of proton pumping. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology. <a href=\"https://doi.org/10.1074/jbc.M308247200\">https://doi.org/10.1074/jbc.M308247200</a>"},"author":[{"full_name":"Holt, Peter","first_name":"Peter","last_name":"Holt"},{"last_name":"Morgan","first_name":"David","full_name":"Morgan, David"},{"full_name":"Sazanov, Leonid A","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-0977-7989","last_name":"Sazanov","first_name":"Leonid A"}],"main_file_link":[{"url":"https://doi.org/10.1074/jbc.M308247200","open_access":"1"}],"volume":278,"date_updated":"2026-05-28T11:41:17Z","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"title":"The location of NuoL and NuoM subunits in the membrane domain of the Escherichia coli Complex I: implications for the mechanism of proton pumping","status":"public","OA_place":"publisher","oa_version":"Published Version","fulldoi":"https://doi.org/10.1074/jbc.M308247200","article_type":"original","DOAJ_listed":"1","article_processing_charge":"No","quality_controlled":"1","pmid":1,"publication_identifier":{"issn":["0021-9258"],"eissn":["1083-351X"]},"OA_type":"gold","intvolume":"       278","issue":"44","_id":"1959","type":"journal_article","doi":"10.1074/jbc.M308247200","publication_status":"published"},{"article_processing_charge":"No","quality_controlled":"1","fulldoi":"https://doi.org/10.1074/jbc.M208959200","article_type":"original","DOAJ_listed":"1","type":"journal_article","doi":"10.1074/jbc.M208959200","publication_status":"published","pmid":1,"publication_identifier":{"eissn":["1083-351X"],"issn":["0021-9258"]},"OA_type":"gold","intvolume":"       278","issue":"21","_id":"1960","year":"2003","extern":"1","external_id":{"pmid":["12637579"]},"publication":"Journal of Biological Chemistry","date_published":"2003-05-23T00:00:00Z","month":"05","scopus_import":"1","page":"19483 - 19491","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","date_updated":"2026-05-28T11:49:06Z","volume":278,"status":"public","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"title":"A role for native lipids in the stabilization and two dimensional crystallization of the Escherichia coli NADH ubiquinone oxidoreductase (complex I)","OA_place":"publisher","oa_version":"Published Version","language":[{"iso":"eng"}],"abstract":[{"text":"NADH-ubiquinone oxidoreductase (complex I or NDH-1) was purified from the BL21 strain of Escherichia coli using an improved procedure. The complex was effectively stabilized by addition of divalent cations and lipids, making the preparation suitable for structural studies. The ubiquinone reductase activity of the enzyme was fully restored by addition of native E. coli lipids. Two different two-dimensional crystal forms, with p2 and p3 symmetry, were obtained using lipids containing native E. coli extracts. Analysis of the crystals showed that they are formed by fully intact complex I in an L-shaped conformation. Activity assays and single particle analysis indicated that complex I maintains this structure in detergent solution and does not adopt a different conformation in the active state. Thus, we provide the first experimental evidence that complex I from E. coli has an L-shape in a lipid bilayer and confirm that this is also the case for the active enzyme in solution. This suggests strongly that bacterial complex I exists in an L-shaped conformation in vivo. Our results also indicate that native lipids play an important role in the activation, stabilization and, as a consequence, crystallization of purified complex I from E. coli.","lang":"eng"}],"oa":1,"date_created":"2018-12-11T11:54:55Z","publist_id":"5125","day":"23","citation":{"short":"L.A. Sazanov, J. Carroll, P. Holt, L. Toime, I. Fearnley, Journal of Biological Chemistry 278 (2003) 19483–19491.","ama":"Sazanov LA, Carroll J, Holt P, Toime L, Fearnley I. A role for native lipids in the stabilization and two dimensional crystallization of the Escherichia coli NADH ubiquinone oxidoreductase (complex I). <i>Journal of Biological Chemistry</i>. 2003;278(21):19483-19491. doi:<a href=\"https://doi.org/10.1074/jbc.M208959200\">10.1074/jbc.M208959200</a>","chicago":"Sazanov, Leonid A, Joe Carroll, Peter Holt, Laurence Toime, and Ian Fearnley. “A Role for Native Lipids in the Stabilization and Two Dimensional Crystallization of the Escherichia Coli NADH Ubiquinone Oxidoreductase (Complex I).” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology, 2003. <a href=\"https://doi.org/10.1074/jbc.M208959200\">https://doi.org/10.1074/jbc.M208959200</a>.","mla":"Sazanov, Leonid A., et al. “A Role for Native Lipids in the Stabilization and Two Dimensional Crystallization of the Escherichia Coli NADH Ubiquinone Oxidoreductase (Complex I).” <i>Journal of Biological Chemistry</i>, vol. 278, no. 21, American Society for Biochemistry and Molecular Biology, 2003, pp. 19483–91, doi:<a href=\"https://doi.org/10.1074/jbc.M208959200\">10.1074/jbc.M208959200</a>.","ista":"Sazanov LA, Carroll J, Holt P, Toime L, Fearnley I. 2003. A role for native lipids in the stabilization and two dimensional crystallization of the Escherichia coli NADH ubiquinone oxidoreductase (complex I). Journal of Biological Chemistry. 278(21), 19483–19491.","apa":"Sazanov, L. A., Carroll, J., Holt, P., Toime, L., &#38; Fearnley, I. (2003). A role for native lipids in the stabilization and two dimensional crystallization of the Escherichia coli NADH ubiquinone oxidoreductase (complex I). <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology. <a href=\"https://doi.org/10.1074/jbc.M208959200\">https://doi.org/10.1074/jbc.M208959200</a>","ieee":"L. A. Sazanov, J. Carroll, P. Holt, L. Toime, and I. Fearnley, “A role for native lipids in the stabilization and two dimensional crystallization of the Escherichia coli NADH ubiquinone oxidoreductase (complex I),” <i>Journal of Biological Chemistry</i>, vol. 278, no. 21. American Society for Biochemistry and Molecular Biology, pp. 19483–19491, 2003."},"author":[{"orcid":"0000-0002-0977-7989","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","full_name":"Sazanov, Leonid A","last_name":"Sazanov","first_name":"Leonid A"},{"full_name":"Carroll, Joe","first_name":"Joe","last_name":"Carroll"},{"first_name":"Peter","last_name":"Holt","full_name":"Holt, Peter"},{"first_name":"Laurence","last_name":"Toime","full_name":"Toime, Laurence"},{"first_name":"Ian","last_name":"Fearnley","full_name":"Fearnley, Ian"}],"publisher":"American Society for Biochemistry and Molecular Biology","main_file_link":[{"url":"https://doi.org/10.1074/jbc.M208959200","open_access":"1"}]},{"oa_version":"Published Version","ddc":["570"],"status":"public","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"title":"The inhibition of glutamate release by metabotropic glutamate receptor 7 affects both [Ca2+]c and cAMP. Evidence for a strong reduction of Ca2+ entry in single nerve terminals","volume":277,"date_updated":"2023-07-25T10:16:44Z","publisher":"American Society for Biochemistry and Molecular Biology","citation":{"ieee":"C. Millán, R. Luján, R. Shigemoto, and J. Sánchez Prieto, “The inhibition of glutamate release by metabotropic glutamate receptor 7 affects both [Ca2+]c and cAMP. Evidence for a strong reduction of Ca2+ entry in single nerve terminals,” <i>Journal of Biological Chemistry</i>, vol. 277, no. 16. American Society for Biochemistry and Molecular Biology, pp. 14092–14101, 2002.","apa":"Millán, C., Luján, R., Shigemoto, R., &#38; Sánchez Prieto, J. (2002). The inhibition of glutamate release by metabotropic glutamate receptor 7 affects both [Ca2+]c and cAMP. Evidence for a strong reduction of Ca2+ entry in single nerve terminals. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology. <a href=\"https://doi.org/10.1074/jbc.M109044200\">https://doi.org/10.1074/jbc.M109044200</a>","chicago":"Millán, Carmelo, Rafael Luján, Ryuichi Shigemoto, and José Sánchez Prieto. “The Inhibition of Glutamate Release by Metabotropic Glutamate Receptor 7 Affects Both [Ca2+]c and CAMP. Evidence for a Strong Reduction of Ca2+ Entry in Single Nerve Terminals.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology, 2002. <a href=\"https://doi.org/10.1074/jbc.M109044200\">https://doi.org/10.1074/jbc.M109044200</a>.","short":"C. Millán, R. Luján, R. Shigemoto, J. Sánchez Prieto, Journal of Biological Chemistry 277 (2002) 14092–14101.","ama":"Millán C, Luján R, Shigemoto R, Sánchez Prieto J. The inhibition of glutamate release by metabotropic glutamate receptor 7 affects both [Ca2+]c and cAMP. Evidence for a strong reduction of Ca2+ entry in single nerve terminals. <i>Journal of Biological Chemistry</i>. 2002;277(16):14092-14101. doi:<a href=\"https://doi.org/10.1074/jbc.M109044200\">10.1074/jbc.M109044200</a>","ista":"Millán C, Luján R, Shigemoto R, Sánchez Prieto J. 2002. The inhibition of glutamate release by metabotropic glutamate receptor 7 affects both [Ca2+]c and cAMP. Evidence for a strong reduction of Ca2+ entry in single nerve terminals. Journal of Biological Chemistry. 277(16), 14092–14101.","mla":"Millán, Carmelo, et al. “The Inhibition of Glutamate Release by Metabotropic Glutamate Receptor 7 Affects Both [Ca2+]c and CAMP. Evidence for a Strong Reduction of Ca2+ Entry in Single Nerve Terminals.” <i>Journal of Biological Chemistry</i>, vol. 277, no. 16, American Society for Biochemistry and Molecular Biology, 2002, pp. 14092–101, doi:<a href=\"https://doi.org/10.1074/jbc.M109044200\">10.1074/jbc.M109044200</a>."},"author":[{"last_name":"Millán","first_name":"Carmelo","full_name":"Millán, Carmelo"},{"full_name":"Luján, Rafael","first_name":"Rafael","last_name":"Luján"},{"first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"},{"first_name":"José","last_name":"Sánchez Prieto","full_name":"Sánchez Prieto, José"}],"publist_id":"4284","date_created":"2018-12-11T11:58:41Z","day":"19","oa":1,"language":[{"iso":"eng"}],"abstract":[{"text":"Metabotropic glutamate receptors (mGluRs) from group III reduce glutamate release. Because these receptors reduce cAMP levels, we explored whether this signaling pathway contributes to release inhibition caused by mGluRs with low affinity for L-2-amino-4-phosphonobutyrate (L-AP4). In biochemical experiments with the population of cerebrocortical nerve terminals we find that L-AP4 (1 mM) inhibited the Ca2+dependent-evoked release of glutamate by 25%. This inhibitory effect was largely prevented by the pertussis toxin but was insensitive to inhibitors of protein kinase C bisindolylmaleimide and protein kinase A H-89. Furthermore, this inhibition was associated with reduction in N-type Ca2+ channel activity in the absence of any detectable change in cAMP levels. In the presence of forskolin, however, L-AP4 decreased the levels of cAMP. The activation of this additional signaling pathway was very efficient in counteracting the facilitation of glutamate release induced either by forskolin or the β-adrenergic receptor agonist isoproterenol. Imaging experiments to measure Ca2+ dynamics in single nerve terminals showed that L-AP4 strongly reduced the Ca2+ response in 28% of the nerve terminals. Moreover, immunochemical experiments showed that 25-35% of the nerve terminals that were immunopositive to synaptophysin were also immunoreactive to the low affinity L-AP4-sensitive mGluR7. Then, mGluR7 mediates the inhibition of glutamate release caused by 1 mM L-AP4, primarily by a strong inhibition of Ca2+ channels, although high cAMP uncovers the receptor ability to decrease cAMP.","lang":"eng"}],"publication":"Journal of Biological Chemistry","file":[{"success":1,"date_created":"2023-07-25T10:13:16Z","access_level":"open_access","checksum":"0290fcbbd9153ec654185b0c856f214c","file_size":2105520,"date_updated":"2023-07-25T10:13:16Z","creator":"alisjak","file_id":"13309","file_name":"2002_JBC_Millan.pdf","content_type":"application/pdf","relation":"main_file"}],"external_id":{"pmid":["11825890"]},"year":"2002","extern":"1","user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","page":"14092 - 14101","date_published":"2002-04-19T00:00:00Z","month":"04","scopus_import":"1","acknowledgement":"We thank Dr. Enrique Castro from Las Palmas University for critical reading of the manuscript and M. Sefton for editorial assistance.","publication_status":"published","doi":"10.1074/jbc.M109044200","type":"journal_article","issue":"16","_id":"2614","intvolume":"       277","publication_identifier":{"issn":["0021-9258"]},"pmid":1,"quality_controlled":"1","has_accepted_license":"1","file_date_updated":"2023-07-25T10:13:16Z","article_processing_charge":"No","fulldoi":"https://doi.org/10.1074/jbc.M109044200","article_type":"original"},{"quality_controlled":"1","article_processing_charge":"No","fulldoi":"https://doi.org/10.1074/jbc.M207531200","article_type":"original","publication_status":"published","type":"journal_article","doi":"10.1074/jbc.M207531200","intvolume":"       277","issue":"49","_id":"2621","pmid":1,"publication_identifier":{"issn":["0021-9258"]},"external_id":{"pmid":["12376542"]},"publication":"Journal of Biological Chemistry","year":"2002","extern":"1","user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","month":"12","date_published":"2002-12-02T00:00:00Z","scopus_import":"1","acknowledgement":"We thank M. Sefton for editorial assistance.","page":"47796 - 47803","oa_version":"Published Version","volume":277,"date_updated":"2023-07-19T07:49:19Z","status":"public","title":"Subtype-specific expression of Group III metabotropic glutamate receptors and Ca2+ channels in single nerve terminals","publist_id":"4277","date_created":"2018-12-11T11:58:43Z","day":"02","citation":{"short":"C. Millán, R. Luján, R. Shigemoto, J. Sánchez Prieto, Journal of Biological Chemistry 277 (2002) 47796–47803.","chicago":"Millán, Carmelo, Rafael Luján, Ryuichi Shigemoto, and José Sánchez Prieto. “Subtype-Specific Expression of Group III Metabotropic Glutamate Receptors and Ca2+ Channels in Single Nerve Terminals.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology, 2002. <a href=\"https://doi.org/10.1074/jbc.M207531200\">https://doi.org/10.1074/jbc.M207531200</a>.","ama":"Millán C, Luján R, Shigemoto R, Sánchez Prieto J. Subtype-specific expression of Group III metabotropic glutamate receptors and Ca2+ channels in single nerve terminals. <i>Journal of Biological Chemistry</i>. 2002;277(49):47796-47803. doi:<a href=\"https://doi.org/10.1074/jbc.M207531200\">10.1074/jbc.M207531200</a>","ista":"Millán C, Luján R, Shigemoto R, Sánchez Prieto J. 2002. Subtype-specific expression of Group III metabotropic glutamate receptors and Ca2+ channels in single nerve terminals. Journal of Biological Chemistry. 277(49), 47796–47803.","mla":"Millán, Carmelo, et al. “Subtype-Specific Expression of Group III Metabotropic Glutamate Receptors and Ca2+ Channels in Single Nerve Terminals.” <i>Journal of Biological Chemistry</i>, vol. 277, no. 49, American Society for Biochemistry and Molecular Biology, 2002, pp. 47796–803, doi:<a href=\"https://doi.org/10.1074/jbc.M207531200\">10.1074/jbc.M207531200</a>.","apa":"Millán, C., Luján, R., Shigemoto, R., &#38; Sánchez Prieto, J. (2002). Subtype-specific expression of Group III metabotropic glutamate receptors and Ca2+ channels in single nerve terminals. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology. <a href=\"https://doi.org/10.1074/jbc.M207531200\">https://doi.org/10.1074/jbc.M207531200</a>","ieee":"C. Millán, R. Luján, R. Shigemoto, and J. Sánchez Prieto, “Subtype-specific expression of Group III metabotropic glutamate receptors and Ca2+ channels in single nerve terminals,” <i>Journal of Biological Chemistry</i>, vol. 277, no. 49. American Society for Biochemistry and Molecular Biology, pp. 47796–47803, 2002."},"publisher":"American Society for Biochemistry and Molecular Biology","author":[{"full_name":"Millán, Carmelo","first_name":"Carmelo","last_name":"Millán"},{"first_name":"Rafael","last_name":"Luján","full_name":"Luján, Rafael"},{"first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sánchez Prieto","first_name":"José","full_name":"Sánchez Prieto, José"}],"language":[{"iso":"eng"}],"abstract":[{"text":"The release properties of glutamatergic nerve terminals are influenced by a number of factors, including the subtype of voltage-dependent calcium channel and the presence of presynaptic autoreceptors. Group III metabotropic glutamate receptors (mGluRs) mediate feedback inhibition of glutamate release by inhibiting Ca2+ channel activity. By imaging Ca2+ in preparations of cerebrocortical nerve terminals, we show that voltage-dependent Ca2+ channels are distributed in a heterogeneous manner in individual nerve terminals. Presynaptic terminals contained only N-type (47.5%; conotoxin GVIA-sensitive), P/Q-type (3.9%; agatoxin IVA-sensitive), or both N- and P/Q-type (42.6%) Ca2+ channels, although the remainder of the terminals (6.1%) were insensitive to these two toxins. In this preparation, two mGluRs with high and low affinity for L(+)-2-amino-4-phosphonobutyrate were identified by immunocytochemistry as mGluR4 and mGluR7, respectively. These receptors were responsible for 22.2 and 24.1% reduction of glutamate release, and they reduced the Ca2+ response in 24.4 and 30.3% of the nerve terminals, respectively. Interestingly, mGluR4 was largely (73.7%) located in nerve terminals expressing both N- and P/Q-type Ca2+ channels, whereas mGluR7 was predominantly (69.9%) located in N-type Ca2+ channel-expressing terminals. This specific coexpression of different group III mGluRs and Ca2+ channels may endow synaptic terminals with distinct release properties and reveals the existence of a high degree of presynaptic heterogeneity.","lang":"eng"}]},{"user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","page":"4435-4445","month":"02","date_published":"2002-02-08T00:00:00Z","keyword":["Cell Biology","Molecular Biology","Biochemistry"],"scopus_import":"1","acknowledgement":"We are grateful to D. E. Clapham, E. Wöll, G. Meyer, and G. Botta for helpful discussion and/or reading of the manuscript. We also thank T. Stiernagle for providing the N2 strain of C. elegans and A. Wimmer and M. Frick for technical assistance","file":[{"content_type":"application/pdf","relation":"main_file","file_name":"2002_JBC_Fuerst.pdf","creator":"alisjak","file_id":"13439","date_updated":"2023-08-01T12:44:09Z","file_size":798920,"checksum":"13abe20f78eb37ab62beb006f62c69b7","date_created":"2023-08-01T12:44:09Z","success":1,"access_level":"open_access"}],"publication":"Journal of Biological Chemistry","external_id":{"pmid":["11706026"]},"year":"2002","extern":"1","publisher":"Elsevier","citation":{"mla":"Fürst, Johannes, et al. “ICln Ion Channel Splice Variants in Caenorhabditis Elegans.” <i>Journal of Biological Chemistry</i>, vol. 277, no. 6, Elsevier, 2002, pp. 4435–45, doi:<a href=\"https://doi.org/10.1074/jbc.m107372200\">10.1074/jbc.m107372200</a>.","ista":"Fürst J, Ritter M, Rudzki J, Danzl JG, Gschwentner M, Scandella E, Jakab M, König M, Oehl B, Lang F, Deetjen P, Paulmichl M. 2002. ICln Ion channel splice variants in Caenorhabditis elegans. Journal of Biological Chemistry. 277(6), 4435–4445.","ama":"Fürst J, Ritter M, Rudzki J, et al. ICln Ion channel splice variants in Caenorhabditis elegans. <i>Journal of Biological Chemistry</i>. 2002;277(6):4435-4445. doi:<a href=\"https://doi.org/10.1074/jbc.m107372200\">10.1074/jbc.m107372200</a>","chicago":"Fürst, Johannes, Markus Ritter, Jakob Rudzki, Johann G Danzl, Martin Gschwentner, Elke Scandella, Martin Jakab, et al. “ICln Ion Channel Splice Variants in Caenorhabditis Elegans.” <i>Journal of Biological Chemistry</i>. Elsevier, 2002. <a href=\"https://doi.org/10.1074/jbc.m107372200\">https://doi.org/10.1074/jbc.m107372200</a>.","short":"J. Fürst, M. Ritter, J. Rudzki, J.G. Danzl, M. Gschwentner, E. Scandella, M. Jakab, M. König, B. Oehl, F. Lang, P. Deetjen, M. Paulmichl, Journal of Biological Chemistry 277 (2002) 4435–4445.","ieee":"J. Fürst <i>et al.</i>, “ICln Ion channel splice variants in Caenorhabditis elegans,” <i>Journal of Biological Chemistry</i>, vol. 277, no. 6. Elsevier, pp. 4435–4445, 2002.","apa":"Fürst, J., Ritter, M., Rudzki, J., Danzl, J. G., Gschwentner, M., Scandella, E., … Paulmichl, M. (2002). ICln Ion channel splice variants in Caenorhabditis elegans. <i>Journal of Biological Chemistry</i>. Elsevier. <a href=\"https://doi.org/10.1074/jbc.m107372200\">https://doi.org/10.1074/jbc.m107372200</a>"},"author":[{"full_name":"Fürst, Johannes","last_name":"Fürst","first_name":"Johannes"},{"last_name":"Ritter","first_name":"Markus","full_name":"Ritter, Markus"},{"full_name":"Rudzki, Jakob","first_name":"Jakob","last_name":"Rudzki"},{"first_name":"Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G"},{"full_name":"Gschwentner, Martin","last_name":"Gschwentner","first_name":"Martin"},{"full_name":"Scandella, Elke","first_name":"Elke","last_name":"Scandella"},{"full_name":"Jakab, Martin","last_name":"Jakab","first_name":"Martin"},{"last_name":"König","first_name":"Matthias","full_name":"König, Matthias"},{"full_name":"Oehl, Bernhard","last_name":"Oehl","first_name":"Bernhard"},{"full_name":"Lang, Florian","last_name":"Lang","first_name":"Florian"},{"first_name":"Peter","last_name":"Deetjen","full_name":"Deetjen, Peter"},{"last_name":"Paulmichl","first_name":"Markus","full_name":"Paulmichl, Markus"}],"date_created":"2023-08-01T12:37:50Z","day":"08","oa":1,"language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"ICln is an ion channel identified by expression cloning using a cDNA library from Madin-Darby canine kidney cells. In all organisms tested so far, only one transcript for the ICln protein could be identified. Here we show that two splice variants of the ICln ion channel can be found in Caenorhabditis elegans. Moreover, we show that these two splice variants of the ICln channel protein, which we termed IClnN1 and IClnN2, can be functionally reconstituted and tested in an artificial lipid bilayer. In these experiments, the IClnN1-induced currents showed no voltage-dependent inactivation, whereas the IClnN2-induced currents fully inactivated at positive potentials. The molecular entity responsible for the voltage-dependent inactivation of IClnN2 is a cluster of positively charged amino acids encoded by exon 2a, which is absent in IClnN1. Our experiments suggest a mechanism of channel inactivation that is similar to the “ball and chain” model proposed for the Shaker potassium channel,i.e. a cluster of positively charged amino acids hinders ion permeation through the channel by a molecular and voltage-dependent interaction at the inner vestibulum of the pore. This hypothesis is supported by the finding that synthetic peptides with the same amino acid sequence as the positive cluster can transform the IClnN1-induced current to the current observed after reconstitution of IClnN2. Furthermore, we show that the nematode ICln gene is embedded in an operon harboring two additional genes, which we termed Nx and Ny. Co-reconstitution of Nx and IClnN2 and functional analysis of the related currents revealed a functional interaction between the two proteins, as evidenced by the fact that the IClnN2-induced current in the presence of Nx was no longer voltage-sensitive. The experiments described indicate that the genome organization in nematodes allows an effective approach for the identification of functional partner proteins of ion channels."}],"oa_version":"Published Version","ddc":["570"],"title":"ICln Ion channel splice variants in Caenorhabditis elegans","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)"},"status":"public","date_updated":"2023-08-01T12:55:54Z","volume":277,"fulldoi":"https://doi.org/10.1074/jbc.m107372200","article_type":"original","quality_controlled":"1","has_accepted_license":"1","file_date_updated":"2023-08-01T12:44:09Z","article_processing_charge":"No","issue":"6","_id":"13438","intvolume":"       277","publication_identifier":{"issn":["0021-9258"]},"pmid":1,"publication_status":"published","doi":"10.1074/jbc.m107372200","type":"journal_article"},{"year":"2001","extern":"1","publication":"Journal of Biological Chemistry","external_id":{"pmid":["11278780"]},"page":"18878 - 18887","date_published":"2001-06-01T00:00:00Z","month":"06","scopus_import":"1","acknowledgement":"We thank Dr. T. Winkler for carrying out flow cytometry analysis, Dr. Simon Goodman for providing cyclic RGD peptides and helpful discussions, and Stefanie Karosi and Thomas Samson for critical review of the manuscript. This work would not have been possible without the expert technical assistance of Friederike Pausch.","user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","title":"Cell adhesion and migration properties of β2-integrin negative polymorphonuclear granulocytes on defined extracellular matrix molecules. Relevance for leukocyte extravasation","status":"public","volume":276,"date_updated":"2023-05-11T12:54:06Z","oa_version":"Published Version","oa":1,"language":[{"iso":"eng"}],"abstract":[{"lang":"eng","text":"Regulated adhesion of leukocytes to the extracellular matrix is essential for transmigration of blood vessels and subsequent migration into the stroma of inflamed tissues. Although beta(2)-integrins play an indisputable role in adhesion of polymorphonuclear granulocytes (PMN) to endothelium, we show here that beta(1)- and beta(3)-integrins but not beta(2)-integrin are essential for the adhesion to and migration on extracellular matrix molecules of the endothelial cell basement membrane and subjacent interstitial matrix. Mouse wild type and beta(2)-integrin null PMN and the progranulocytic cell line 32DC13 were employed in in vitro adhesion and migration assays using extracellular matrix molecules expressed at sites of extravasation in vivo, in particular the endothelial cell laminins 8 and 10. Wild type and beta(2)-integrin null PMN showed the same pattern of ECM binding, indicating that beta(2)-integrins do not mediate specific adhesion of PMN to the extracellular matrix molecules tested; binding was observed to the interstitial matrix molecules, fibronectin and vitronectin, via integrins alpha(5)beta(1) and alpha(v)beta(3), respectively; to laminin 10 via alpha(6)beta(1); but not to laminins 1, 2, and 8, collagen type I and IV, perlecan, or tenascin-C. PMN binding to laminins 1, 2, and 8 could not be induced despite surface expression of functionally active integrin alpha(6)beta(1), a major laminin receptor, demonstrating that expression of alpha(6)beta(1) alone is insufficient for ligand binding and suggesting the involvement of accessory factors. Nevertheless, laminins 1, 8, and 10 supported PMN migration, indicating that differential cellular signaling via laminins is independent of the extent of adhesion. The data demonstrate that adhesive and nonadhesive interactions with components of the endothelial cell basement membrane and subjacent interstitium play decisive roles in controlling PMN movement into sites of inflammation and illustrate that beta(2)-integrins are not essential for such interactions."}],"publisher":"American Society for Biochemistry and Molecular Biology","citation":{"apa":"Sixt, M. K., Hallmann, R., Wendler, O., Scharffetter Kochanek, K., &#38; Sorokin, L. (2001). Cell adhesion and migration properties of β2-integrin negative polymorphonuclear granulocytes on defined extracellular matrix molecules. Relevance for leukocyte extravasation. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology. <a href=\"https://doi.org/10.1074/jbc.M010898200\">https://doi.org/10.1074/jbc.M010898200</a>","ieee":"M. K. Sixt, R. Hallmann, O. Wendler, K. Scharffetter Kochanek, and L. Sorokin, “Cell adhesion and migration properties of β2-integrin negative polymorphonuclear granulocytes on defined extracellular matrix molecules. Relevance for leukocyte extravasation,” <i>Journal of Biological Chemistry</i>, vol. 276, no. 22. American Society for Biochemistry and Molecular Biology, pp. 18878–18887, 2001.","chicago":"Sixt, Michael K, Rupert Hallmann, Olaf Wendler, Karin Scharffetter Kochanek, and Lydia Sorokin. “Cell Adhesion and Migration Properties of Β2-Integrin Negative Polymorphonuclear Granulocytes on Defined Extracellular Matrix Molecules. Relevance for Leukocyte Extravasation.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology, 2001. <a href=\"https://doi.org/10.1074/jbc.M010898200\">https://doi.org/10.1074/jbc.M010898200</a>.","ama":"Sixt MK, Hallmann R, Wendler O, Scharffetter Kochanek K, Sorokin L. Cell adhesion and migration properties of β2-integrin negative polymorphonuclear granulocytes on defined extracellular matrix molecules. Relevance for leukocyte extravasation. <i>Journal of Biological Chemistry</i>. 2001;276(22):18878-18887. doi:<a href=\"https://doi.org/10.1074/jbc.M010898200\">10.1074/jbc.M010898200</a>","short":"M.K. Sixt, R. Hallmann, O. Wendler, K. Scharffetter Kochanek, L. Sorokin, Journal of Biological Chemistry 276 (2001) 18878–18887.","ista":"Sixt MK, Hallmann R, Wendler O, Scharffetter Kochanek K, Sorokin L. 2001. Cell adhesion and migration properties of β2-integrin negative polymorphonuclear granulocytes on defined extracellular matrix molecules. Relevance for leukocyte extravasation. Journal of Biological Chemistry. 276(22), 18878–18887.","mla":"Sixt, Michael K., et al. “Cell Adhesion and Migration Properties of Β2-Integrin Negative Polymorphonuclear Granulocytes on Defined Extracellular Matrix Molecules. Relevance for Leukocyte Extravasation.” <i>Journal of Biological Chemistry</i>, vol. 276, no. 22, American Society for Biochemistry and Molecular Biology, 2001, pp. 18878–87, doi:<a href=\"https://doi.org/10.1074/jbc.M010898200\">10.1074/jbc.M010898200</a>."},"author":[{"last_name":"Sixt","first_name":"Michael K","orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K"},{"last_name":"Hallmann","first_name":"Rupert","full_name":"Hallmann, Rupert"},{"full_name":"Wendler, Olaf","last_name":"Wendler","first_name":"Olaf"},{"first_name":"Karin","last_name":"Scharffetter Kochanek","full_name":"Scharffetter Kochanek, Karin"},{"last_name":"Sorokin","first_name":"Lydia","full_name":"Sorokin, Lydia"}],"main_file_link":[{"url":"https://www.sciencedirect.com/science/article/pii/S0021925819670134?via%3Dihub","open_access":"1"}],"publist_id":"2199","date_created":"2018-12-11T12:05:56Z","day":"01","article_processing_charge":"No","quality_controlled":"1","fulldoi":"https://doi.org/10.1074/jbc.M010898200","article_type":"original","doi":"10.1074/jbc.M010898200","type":"journal_article","publication_status":"published","publication_identifier":{"issn":["0021-9258"]},"pmid":1,"issue":"22","_id":"3928","intvolume":"       276"},{"abstract":[{"lang":"eng","text":"The prohormone convertases (PCs) are an evolutionarily ancient group of proteases required for the maturation of neuropeptide and peptide hormone precursors. In Drosophila melanogaster, the homolog of prohormone convertase 2, dPC2 (amontillado), is required for normal hatching behavior, and immunoblotting data indicate that flies express 80- and 75-kDa forms of this protein. Because mouse PC2 (mPC2) requires 7B2, a helper protein for productive maturation, we searched the fly data base for the 7B2 signature motif PPNPCP and identified an expressed sequence tag clone encoding the entire open reading frame for this protein. dPC2 and d7B2 cDNAs were subcloned into expression vectors for transfection into HEK-293 cells; mPC2 and rat 7B2 were used as controls. Although active mPC2 was detected in medium in the presence of either d7B2 or r7B2, dPC2 showed no proteolytic activity upon coexpression of either d7B2 or r7B2. Labeling experiments showed that dPC2 was synthesized but not secreted from HEK-293 cells. However, when dPC2 and either d7B2 or r7B2 were coexpressed in Drosophila S2 cells, abundant immunoreactive dPC2 was secreted into the medium, coincident with the appearance of PC2 activity. Expression and secretion of dPC2 enzyme activity thus appears to require insect cell-specific posttranslational processing events. The significant differences in the cell biology of the insect and mammalian enzymes, with 7B2 absolutely required for secretion of dPC2 and zymogen conversion occurring intracellularly in the case of dPC2 but not mPC2, support the idea that the Drosophila enzyme has specific requirements for maturation and secretion that can be met only in insect cells."}],"language":[{"iso":"eng"}],"oa":1,"day":"09","publist_id":"3546","date_created":"2018-12-11T12:01:40Z","main_file_link":[{"url":"https://www.sciencedirect.com/science/article/pii/S0021925819833215?via%3Dihub","open_access":"1"}],"citation":{"ista":"Hwang J, Siekhaus DE, Fuller R, Taghert P, Lindberg I. 2000. Interaction of Drosophila melanogaster prohormone convertase 2 and 7B2: Insect cell specific processing and secretion. Journal of Biological Chemistry. 275(23), 17886–17893.","mla":"Hwang, Jae, et al. “Interaction of Drosophila Melanogaster Prohormone Convertase 2 and 7B2: Insect Cell Specific Processing and Secretion.” <i>Journal of Biological Chemistry</i>, vol. 275, no. 23, American Society for Biochemistry and Molecular Biology, 2000, pp. 17886–93, doi:<a href=\"https://doi.org/10.1074/jbc.M000032200 \">10.1074/jbc.M000032200 </a>.","short":"J. Hwang, D.E. Siekhaus, R. Fuller, P. Taghert, I. Lindberg, Journal of Biological Chemistry 275 (2000) 17886–17893.","chicago":"Hwang, Jae, Daria E Siekhaus, Robert Fuller, Paul Taghert, and Iris Lindberg. “Interaction of Drosophila Melanogaster Prohormone Convertase 2 and 7B2: Insect Cell Specific Processing and Secretion.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology, 2000. <a href=\"https://doi.org/10.1074/jbc.M000032200 \">https://doi.org/10.1074/jbc.M000032200 </a>.","ama":"Hwang J, Siekhaus DE, Fuller R, Taghert P, Lindberg I. Interaction of Drosophila melanogaster prohormone convertase 2 and 7B2: Insect cell specific processing and secretion. <i>Journal of Biological Chemistry</i>. 2000;275(23):17886-17893. doi:<a href=\"https://doi.org/10.1074/jbc.M000032200 \">10.1074/jbc.M000032200 </a>","ieee":"J. Hwang, D. E. Siekhaus, R. Fuller, P. Taghert, and I. Lindberg, “Interaction of Drosophila melanogaster prohormone convertase 2 and 7B2: Insect cell specific processing and secretion,” <i>Journal of Biological Chemistry</i>, vol. 275, no. 23. American Society for Biochemistry and Molecular Biology, pp. 17886–17893, 2000.","apa":"Hwang, J., Siekhaus, D. E., Fuller, R., Taghert, P., &#38; Lindberg, I. (2000). Interaction of Drosophila melanogaster prohormone convertase 2 and 7B2: Insect cell specific processing and secretion. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology. <a href=\"https://doi.org/10.1074/jbc.M000032200 \">https://doi.org/10.1074/jbc.M000032200 </a>"},"publisher":"American Society for Biochemistry and Molecular Biology","author":[{"full_name":"Hwang, Jae","first_name":"Jae","last_name":"Hwang"},{"first_name":"Daria E","last_name":"Siekhaus","full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Fuller, Robert","last_name":"Fuller","first_name":"Robert"},{"full_name":"Taghert, Paul","last_name":"Taghert","first_name":"Paul"},{"full_name":"Lindberg, Iris","last_name":"Lindberg","first_name":"Iris"}],"volume":275,"date_updated":"2023-05-03T08:47:13Z","status":"public","title":"Interaction of Drosophila melanogaster prohormone convertase 2 and 7B2: Insect cell specific processing and secretion","oa_version":"Published Version","scopus_import":"1","acknowledgement":"This work was supported by National Institutes of Health Grants DK49703 (to I. L.), NS21749 (to P. H. T.), and GM39697 (to R. S. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 10749852. We thank members of the Lindberg laboratory and Laurent Muller for helpful comments, Bin Tu for construction of the C. elegans PC2 expression vector, and Joelle Finley for assistance with cell culture.","month":"06","date_published":"2000-06-09T00:00:00Z","page":"17886 - 17893","user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","extern":"1","year":"2000","external_id":{"pmid":["10749852"]},"publication":"Journal of Biological Chemistry","pmid":1,"publication_identifier":{"issn":["0021-9258"]},"intvolume":"       275","_id":"3149","issue":"23","type":"journal_article","doi":"10.1074/jbc.M000032200 ","publication_status":"published","article_type":"original","fulldoi":"https://doi.org/10.1074/jbc.M000032200 ","article_processing_charge":"No","quality_controlled":"1"},{"day":"14","date_created":"2018-12-11T12:07:25Z","publist_id":"1941","main_file_link":[{"url":"https://www.sciencedirect.com/science/article/pii/S0021925817421867?via%3Dihub","open_access":"1"}],"publisher":"American Society for Biochemistry and Molecular Biology","author":[{"first_name":"Axel","last_name":"Leingärtner","full_name":"Leingärtner, Axel"},{"last_name":"Heisenberg","first_name":"Carl-Philipp J","full_name":"Heisenberg, Carl-Philipp J","orcid":"0000-0002-0912-4566","id":"39427864-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kolbeck, Roland","first_name":"Roland","last_name":"Kolbeck"},{"last_name":"Thoenen","first_name":"Hans","full_name":"Thoenen, Hans"},{"full_name":"Lindholm, Dan","first_name":"Dan","last_name":"Lindholm"}],"citation":{"apa":"Leingärtner, A., Heisenberg, C.-P. J., Kolbeck, R., Thoenen, H., &#38; Lindholm, D. (1994). Brain-derived neurotrophic factor increases neurotrophin-3 expression in cerebellar granule neurons. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology. <a href=\"https://doi.org/10.1016/s0021-9258(17)42186-7\">https://doi.org/10.1016/s0021-9258(17)42186-7</a>","ieee":"A. Leingärtner, C.-P. J. Heisenberg, R. Kolbeck, H. Thoenen, and D. Lindholm, “Brain-derived neurotrophic factor increases neurotrophin-3 expression in cerebellar granule neurons,” <i>Journal of Biological Chemistry</i>, vol. 269, no. 2. American Society for Biochemistry and Molecular Biology, pp. 828–830, 1994.","chicago":"Leingärtner, Axel, Carl-Philipp J Heisenberg, Roland Kolbeck, Hans Thoenen, and Dan Lindholm. “Brain-Derived Neurotrophic Factor Increases Neurotrophin-3 Expression in Cerebellar Granule Neurons.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology, 1994. <a href=\"https://doi.org/10.1016/s0021-9258(17)42186-7\">https://doi.org/10.1016/s0021-9258(17)42186-7</a>.","short":"A. Leingärtner, C.-P.J. Heisenberg, R. Kolbeck, H. Thoenen, D. Lindholm, Journal of Biological Chemistry 269 (1994) 828–830.","ama":"Leingärtner A, Heisenberg C-PJ, Kolbeck R, Thoenen H, Lindholm D. Brain-derived neurotrophic factor increases neurotrophin-3 expression in cerebellar granule neurons. <i>Journal of Biological Chemistry</i>. 1994;269(2):828-830. doi:<a href=\"https://doi.org/10.1016/s0021-9258(17)42186-7\">10.1016/s0021-9258(17)42186-7</a>","ista":"Leingärtner A, Heisenberg C-PJ, Kolbeck R, Thoenen H, Lindholm D. 1994. Brain-derived neurotrophic factor increases neurotrophin-3 expression in cerebellar granule neurons. Journal of Biological Chemistry. 269(2), 828–830.","mla":"Leingärtner, Axel, et al. “Brain-Derived Neurotrophic Factor Increases Neurotrophin-3 Expression in Cerebellar Granule Neurons.” <i>Journal of Biological Chemistry</i>, vol. 269, no. 2, American Society for Biochemistry and Molecular Biology, 1994, pp. 828–30, doi:<a href=\"https://doi.org/10.1016/s0021-9258(17)42186-7\">10.1016/s0021-9258(17)42186-7</a>."},"abstract":[{"lang":"eng","text":"Neurotrophin-3 (NT-3) is a member of the neurotrophin gene family and is highly expressed in the developing rat cerebellum. Here we show that brain-derived neurotrophic factor (BDNF) increased by approximately 10-fold the NT-3 mRNA levels in cultured cerebellar granule neurons isolated from postnatal rats, whereas nerve growth factor (NGF) and NT-3 itself had no effect. The effect of BDNF was additive to that of triiodothyronine (T3), which also increased NT-3 mRNA in these neurons. The drug K252a inhibited the BDNF-mediated stimulation of NT-3 expression, suggesting an involvement of trkB receptors. Nuclear run-on experiments showed that BDNF enhanced NT-3 transcription, whereas the stability of NT-3 mRNA remained unchanged. The data presented are the first demonstration that one neurotrophin regulates the expression of another and provide evidence that NT-3 production in granule neurons is regulated by both BDNF and T3."}],"language":[{"iso":"eng"}],"oa":1,"oa_version":"None","volume":269,"date_updated":"2022-06-02T10:23:48Z","title":"Brain-derived neurotrophic factor increases neurotrophin-3 expression in cerebellar granule neurons","status":"public","user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","scopus_import":"1","acknowledgement":"We thank Dorothea Stratmann and Karin Angermayer for skillful technical assistance.","date_published":"1994-01-14T00:00:00Z","month":"01","page":"828 - 830","publication":"Journal of Biological Chemistry","extern":"1","year":"1994","intvolume":"       269","_id":"4179","issue":"2","publication_identifier":{"issn":["0021-9258"],"eissn":["1083-351X"]},"publication_status":"published","type":"journal_article","doi":"10.1016/s0021-9258(17)42186-7","article_type":"original","fulldoi":"https://doi.org/10.1016/s0021-9258(17)42186-7","quality_controlled":"1","article_processing_charge":"No"},{"article_type":"original","fulldoi":"https://doi.org/10.1016/S0021-9258(19)50280-0","article_processing_charge":"No","quality_controlled":"1","pmid":1,"publication_identifier":{"issn":["0021-9258"]},"intvolume":"       268","_id":"2536","issue":"16","type":"journal_article","doi":"10.1016/S0021-9258(19)50280-0","publication_status":"published","scopus_import":"1","acknowledgement":"This work was supported in part by research grants from the Ministry of Education, Science and Culture of Japan, the Ministry of Health and Welfare, the Yamanouchi Foundation for Research on Metabolic Disorders, the Uehara Memorial Foundation, and the Inamori Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. \r\n\r\nWe are grateful to Akira Uesugi for photographic assistance.","date_published":"1993-06-05T00:00:00Z","month":"06","page":"11868 - 11873","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","extern":"1","year":"1993","external_id":{"pmid":["8389366"]},"publication":"Journal of Biological Chemistry","abstract":[{"text":"A cDNA clone for a new metabotropic glutamate receptor, termed mGluR6, was isolated from a rat retinal cDNA library by cross-hybridization with the previously isolated cDNA clone for a metabotropic glutamate receptor. The cloned mGluR6 subtype consists of 871 amino acid residues and exhibits a structural architecture common to the metabotropic receptor family, possessing a large extracellular domain preceding the seven putative membrane-spanning domains. mGluR6 shows the highest sequence similarity to mGluR4 among the metabotropic receptor subtypes and inhibits the forskolin- stimulated cyclic AMP accumulation in Chinese hamster ovary cells transfected with the cloned cDNA. mGluR6 potently reacts with L-2-amino-4- phosphonobutyrate (L-AP4) and L-serine-O-phosphate, and the potencies of these compounds are one order of magnitude greater than that of L-glutamate. Blot and in situ hybridization analyses indicated that mGluR6 mRNA is restrictedly expressed in the inner nuclear layer of the retina where ON- bipolar cells are distributed. The metabotropic receptor that responds strongly to L-AP4 and L-serine-O-phosphate in ON-bipolar cells is known to mediate glutamate synaptic transmission between photoreceptor cells and ON- bipolar cells. On the basis of the agonist selectivity of mGluR6 and its specific expression in retinal cells, the physiological role of this receptor subtype in the visual system is discussed.","lang":"eng"}],"language":[{"iso":"eng"}],"oa":1,"day":"05","date_created":"2018-12-11T11:58:15Z","publist_id":"4362","main_file_link":[{"url":"https://doi.org/10.1016/S0021-9258(19)50280-0","open_access":"1"}],"author":[{"first_name":"Yoshiaki","last_name":"Nakajima","full_name":"Nakajima, Yoshiaki"},{"last_name":"Iwakabe","first_name":"Hideki","full_name":"Iwakabe, Hideki"},{"first_name":"Chihiro","last_name":"Akazawa","full_name":"Akazawa, Chihiro"},{"first_name":"Hiroyuki","last_name":"Nawa","full_name":"Nawa, Hiroyuki"},{"first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"},{"first_name":"Noboru","last_name":"Mizuno","full_name":"Mizuno, Noboru"},{"full_name":"Nakanishi, Shigetada","last_name":"Nakanishi","first_name":"Shigetada"}],"publisher":"American Society for Biochemistry and Molecular Biology","citation":{"ieee":"Y. Nakajima <i>et al.</i>, “Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4- phosphonobutyrate,” <i>Journal of Biological Chemistry</i>, vol. 268, no. 16. American Society for Biochemistry and Molecular Biology, pp. 11868–11873, 1993.","apa":"Nakajima, Y., Iwakabe, H., Akazawa, C., Nawa, H., Shigemoto, R., Mizuno, N., &#38; Nakanishi, S. (1993). Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4- phosphonobutyrate. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology. <a href=\"https://doi.org/10.1016/S0021-9258(19)50280-0\">https://doi.org/10.1016/S0021-9258(19)50280-0</a>","mla":"Nakajima, Yoshiaki, et al. “Molecular Characterization of a Novel Retinal Metabotropic Glutamate Receptor MGluR6 with a High Agonist Selectivity for L-2-Amino-4- Phosphonobutyrate.” <i>Journal of Biological Chemistry</i>, vol. 268, no. 16, American Society for Biochemistry and Molecular Biology, 1993, pp. 11868–73, doi:<a href=\"https://doi.org/10.1016/S0021-9258(19)50280-0\">10.1016/S0021-9258(19)50280-0</a>.","ista":"Nakajima Y, Iwakabe H, Akazawa C, Nawa H, Shigemoto R, Mizuno N, Nakanishi S. 1993. Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4- phosphonobutyrate. Journal of Biological Chemistry. 268(16), 11868–11873.","chicago":"Nakajima, Yoshiaki, Hideki Iwakabe, Chihiro Akazawa, Hiroyuki Nawa, Ryuichi Shigemoto, Noboru Mizuno, and Shigetada Nakanishi. “Molecular Characterization of a Novel Retinal Metabotropic Glutamate Receptor MGluR6 with a High Agonist Selectivity for L-2-Amino-4- Phosphonobutyrate.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology, 1993. <a href=\"https://doi.org/10.1016/S0021-9258(19)50280-0\">https://doi.org/10.1016/S0021-9258(19)50280-0</a>.","ama":"Nakajima Y, Iwakabe H, Akazawa C, et al. Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4- phosphonobutyrate. <i>Journal of Biological Chemistry</i>. 1993;268(16):11868-11873. doi:<a href=\"https://doi.org/10.1016/S0021-9258(19)50280-0\">10.1016/S0021-9258(19)50280-0</a>","short":"Y. Nakajima, H. Iwakabe, C. Akazawa, H. Nawa, R. Shigemoto, N. Mizuno, S. Nakanishi, Journal of Biological Chemistry 268 (1993) 11868–11873."},"date_updated":"2022-04-26T06:56:15Z","volume":268,"status":"public","title":"Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4- phosphonobutyrate","oa_version":"Published Version"},{"article_processing_charge":"No","quality_controlled":"1","fulldoi":"https://doi.org/10.1016/s0021-9258(18)53849-7 ","article_type":"original","type":"journal_article","doi":"10.1016/s0021-9258(18)53849-7 ","publication_status":"published","pmid":1,"publication_identifier":{"issn":["0021-9258"]},"intvolume":"       268","issue":"4","_id":"2539","year":"1993","extern":"1","external_id":{"pmid":["8428958"]},"publication":"Journal of Biological Chemistry","month":"02","date_published":"1993-02-05T00:00:00Z","acknowledgement":"This work was supported in part by research grants from the Ministry of Education, Science, and Culture of Japan, the Ministry of Health and Welfare of Japan, the Senri Life Science Foundation, and Yamanouchi Foundation for Research on Metabolic Disorders. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “aduertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.","scopus_import":"1","page":"2836 - 2843","user_id":"ea97e931-d5af-11eb-85d4-e6957dddbf17","date_updated":"2022-03-31T14:29:17Z","volume":268,"title":"Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits","status":"public","oa_version":"Published Version","language":[{"iso":"eng"}],"abstract":[{"text":"cDNA clones for four different N-methyl-D-aspartate (NMDA) receptor subunits (NMDAR2A-NMDAR2D) were isolated through polymerase chain reactions followed by molecular screening of a rat brain cDNA library. These subunits are only about 15% identical with the key subunit of the NMDA receptor (NMDAR1) but are highly homologous (~50% homology) with one another. They also commonly possess large hydrophilic domains at both amino- and carboxyl- terminal sides of the four putative transmembrane segments. NMDAR2A and NMDAR2C expressed individually in Xenopus oocytes showed no electrophysiological response to agonists. However, these subunits in combined expression with NMDAR1 markedly potentiated the NMDAR1 activity and produced functional variability in the affinity of agonists, the effectiveness of antagonists, and the sensitivity to Mg2+ blockade. Thus, NMDAR1 is essential for the function of the NMDA receptor, and multiple NMDAR2 subunits potentiate and differentiate the function of the NMDA receptor by forming different heteromeric configurations with NMDAR1. Northern blotting and in situ hybridization analyses revealed that the expressions of individual mRNAs for the NMDAR2 subunits overlap in some brain regions but are also specialized in many other regions. This investigation demonstrates the anatomical and functional differences of the NMDAR2 subunits, which provide the molecular basis for the functional diversity of the NMDA receptor.","lang":"eng"}],"oa":1,"date_created":"2018-12-11T11:58:16Z","publist_id":"4360","day":"05","publisher":"American Society for Biochemistry and Molecular Biology","citation":{"ama":"Ishii T, Moriyoshi K, Sugihara H, et al. Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits. <i>Journal of Biological Chemistry</i>. 1993;268(4):2836-2843. doi:<a href=\"https://doi.org/10.1016/s0021-9258(18)53849-7 \">10.1016/s0021-9258(18)53849-7 </a>","short":"T. Ishii, K. Moriyoshi, H. Sugihara, K. Sakurada, H. Kadotani, M. Yokoi, C. Akazawa, R. Shigemoto, N. Mizuno, M. Masu, S. Nakanishi, Journal of Biological Chemistry 268 (1993) 2836–2843.","chicago":"Ishii, Takahiro, Koki Moriyoshi, Hidemitsu Sugihara, Kazuhir Sakurada, Hiroshi Kadotani, Mineto Yokoi, Chihiro Akazawa, et al. “Molecular Characterization of the Family of the N-Methyl-D-Aspartate Receptor Subunits.” <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology, 1993. <a href=\"https://doi.org/10.1016/s0021-9258(18)53849-7 \">https://doi.org/10.1016/s0021-9258(18)53849-7 </a>.","ista":"Ishii T, Moriyoshi K, Sugihara H, Sakurada K, Kadotani H, Yokoi M, Akazawa C, Shigemoto R, Mizuno N, Masu M, Nakanishi S. 1993. Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits. Journal of Biological Chemistry. 268(4), 2836–2843.","mla":"Ishii, Takahiro, et al. “Molecular Characterization of the Family of the N-Methyl-D-Aspartate Receptor Subunits.” <i>Journal of Biological Chemistry</i>, vol. 268, no. 4, American Society for Biochemistry and Molecular Biology, 1993, pp. 2836–43, doi:<a href=\"https://doi.org/10.1016/s0021-9258(18)53849-7 \">10.1016/s0021-9258(18)53849-7 </a>.","apa":"Ishii, T., Moriyoshi, K., Sugihara, H., Sakurada, K., Kadotani, H., Yokoi, M., … Nakanishi, S. (1993). Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits. <i>Journal of Biological Chemistry</i>. American Society for Biochemistry and Molecular Biology. <a href=\"https://doi.org/10.1016/s0021-9258(18)53849-7 \">https://doi.org/10.1016/s0021-9258(18)53849-7 </a>","ieee":"T. Ishii <i>et al.</i>, “Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits,” <i>Journal of Biological Chemistry</i>, vol. 268, no. 4. American Society for Biochemistry and Molecular Biology, pp. 2836–2843, 1993."},"author":[{"full_name":"Ishii, Takahiro","last_name":"Ishii","first_name":"Takahiro"},{"full_name":"Moriyoshi, Koki","first_name":"Koki","last_name":"Moriyoshi"},{"full_name":"Sugihara, Hidemitsu","last_name":"Sugihara","first_name":"Hidemitsu"},{"full_name":"Sakurada, Kazuhir","first_name":"Kazuhir","last_name":"Sakurada"},{"first_name":"Hiroshi","last_name":"Kadotani","full_name":"Kadotani, Hiroshi"},{"full_name":"Yokoi, Mineto","first_name":"Mineto","last_name":"Yokoi"},{"first_name":"Chihiro","last_name":"Akazawa","full_name":"Akazawa, Chihiro"},{"first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444"},{"full_name":"Mizuno, Noboru","last_name":"Mizuno","first_name":"Noboru"},{"full_name":"Masu, Masayuki","last_name":"Masu","first_name":"Masayuki"},{"last_name":"Nakanishi","first_name":"Shigetada","full_name":"Nakanishi, Shigetada"}],"main_file_link":[{"open_access":"1","url":"https://www.jbc.org/article/S0021-9258(18)53849-7/fulltext"}]}]