[{"_id":"18621","external_id":{"pmid":["37721334"]},"doi":"10.1242/dev.201208","month":"09","article_processing_charge":"No","publication_identifier":{"issn":["0950-1991"],"eissn":["1477-9129"]},"year":"2023","intvolume":"       150","title":"Convertase-dependent regulation of membrane-tethered and secreted ligands tunes dendrite adhesion","citation":{"ama":"Ramirez N, Belalcazar HM, Rahman M, Trivedi M, Tang LTH, Bülow HE. Convertase-dependent regulation of membrane-tethered and secreted ligands tunes dendrite adhesion. <i>Development</i>. 2023;150(18). doi:<a href=\"https://doi.org/10.1242/dev.201208\">10.1242/dev.201208</a>","ista":"Ramirez N, Belalcazar HM, Rahman M, Trivedi M, Tang LTH, Bülow HE. 2023. Convertase-dependent regulation of membrane-tethered and secreted ligands tunes dendrite adhesion. Development. 150(18).","chicago":"Ramirez, Nelson, Helen M. Belalcazar, Maisha Rahman, Meera Trivedi, Leo T. H. Tang, and Hannes E. Bülow. “Convertase-Dependent Regulation of Membrane-Tethered and Secreted Ligands Tunes Dendrite Adhesion.” <i>Development</i>. The Company of Biologists, 2023. <a href=\"https://doi.org/10.1242/dev.201208\">https://doi.org/10.1242/dev.201208</a>.","mla":"Ramirez, Nelson, et al. “Convertase-Dependent Regulation of Membrane-Tethered and Secreted Ligands Tunes Dendrite Adhesion.” <i>Development</i>, vol. 150, no. 18, The Company of Biologists, 2023, doi:<a href=\"https://doi.org/10.1242/dev.201208\">10.1242/dev.201208</a>.","ieee":"N. Ramirez, H. M. Belalcazar, M. Rahman, M. Trivedi, L. T. H. Tang, and H. E. Bülow, “Convertase-dependent regulation of membrane-tethered and secreted ligands tunes dendrite adhesion,” <i>Development</i>, vol. 150, no. 18. The Company of Biologists, 2023.","short":"N. Ramirez, H.M. Belalcazar, M. Rahman, M. Trivedi, L.T.H. Tang, H.E. Bülow, Development 150 (2023).","apa":"Ramirez, N., Belalcazar, H. M., Rahman, M., Trivedi, M., Tang, L. T. H., &#38; Bülow, H. E. (2023). Convertase-dependent regulation of membrane-tethered and secreted ligands tunes dendrite adhesion. <i>Development</i>. The Company of Biologists. <a href=\"https://doi.org/10.1242/dev.201208\">https://doi.org/10.1242/dev.201208</a>"},"publication":"Development","article_type":"original","status":"public","publisher":"The Company of Biologists","author":[{"id":"39831956-E4FE-11E9-85DE-0DC7E5697425","full_name":"Ramirez, Nelson","first_name":"Nelson","last_name":"Ramirez"},{"first_name":"Helen M.","last_name":"Belalcazar","full_name":"Belalcazar, Helen M."},{"full_name":"Rahman, Maisha","first_name":"Maisha","last_name":"Rahman"},{"last_name":"Trivedi","first_name":"Meera","full_name":"Trivedi, Meera"},{"last_name":"Tang","first_name":"Leo T. H.","full_name":"Tang, Leo T. H."},{"last_name":"Bülow","first_name":"Hannes E.","full_name":"Bülow, Hannes E."}],"date_updated":"2024-12-09T11:43:40Z","date_published":"2023-09-18T00:00:00Z","has_accepted_license":"1","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file":[{"date_updated":"2024-12-04T22:12:04Z","creator":"nramirez","checksum":"d2158dc56db50457e6404c4afec4401c","relation":"main_file","file_name":"dev201208.pdf","file_size":9559527,"date_created":"2024-12-04T22:12:04Z","file_id":"18624","content_type":"application/pdf","success":1,"access_level":"open_access"}],"oa_version":"Published Version","type":"journal_article","publication_status":"published","volume":150,"extern":"1","file_date_updated":"2024-12-04T22:12:04Z","OA_place":"publisher","pmid":1,"language":[{"iso":"eng"}],"OA_type":"hybrid","scopus_import":"1","day":"18","issue":"18","quality_controlled":"1","abstract":[{"lang":"eng","text":"During neural development, cellular adhesion is crucial for interactions among and between neurons and surrounding tissues. This function is mediated by conserved cell adhesion molecules, which are tightly regulated to allow for coordinated neuronal outgrowth. Here, we show that the proprotein convertase KPC-1 (homolog of mammalian furin) regulates the Menorin adhesion complex during development of PVD dendritic arbors in Caenorhabditis elegans. We found a finely regulated antagonistic balance between PVD-expressed KPC-1 and the epidermally expressed putative cell adhesion molecule MNR-1 (Menorin). Genetically, partial loss of mnr-1 suppressed partial loss of kpc-1, and both loss of kpc-1 and transgenic overexpression of mnr-1 resulted in indistinguishable phenotypes in PVD dendrites. This balance regulated cell-surface localization of the DMA-1 leucine-rich transmembrane receptor in PVD neurons. Lastly, kpc-1 mutants showed increased amounts of MNR-1 and decreased amounts of muscle-derived LECT-2 (Chondromodulin II), which is also part of the Menorin adhesion complex. These observations suggest that KPC-1 in PVD neurons directly or indirectly controls the abundance of proteins of the Menorin adhesion complex from adjacent tissues, thereby providing negative feedback from the dendrite to the instructive cues of surrounding tissues."}],"oa":1,"acknowledgement":"We thank members of the Bülow laboratory for comments on the manuscript and discussions throughout the course of this work; and Ryan Peer and William Corman for their initial help with the modifier genetic screen. We acknowledge the Genomics Core facility and the Advanced Imaging Facility at Albert Einstein College of Medicine for help during these studies. We are grateful to Kang Shen, David Miller and the Caenorhabditis Genetics Center (which is funded by National Institutes of Health Office of Research Infrastructure Programs P40OD0104400) for some of the strains used in this study, and Lhisia Chen for the anti-SAX-7 antibody.\r\nThis work was supported by grants from the National Institutes of Health (F31NS100370 to M.R.; T32GM007288 and F31NS111939 to M.T.; R01NS096672, R21NS081505 and R01NS129992 to H.E.B.; and P30HD071593 to Albert Einstein College of Medicine). N.J.R.-S. was the recipient of a Colciencias-Fulbright Fellowship [funded by Departamento Administrativo de Ciencia, Tecnología e Innovación (COLCIENCIAS) and Fulbright Colombia], L.T.H.T. of a Croucher Foundation Fellowship, and H.E.B. of an Irma T. Hirschl Trust/Monique Weill-Caulier Trust research fellowship. Open Access funding provided by Albert Einstein College of Medicine, Yeshiva University. Deposited in PMC for immediate release.","fulldoi":"https://doi.org/10.1242/dev.201208","date_created":"2024-12-04T22:02:52Z","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)"}},{"scopus_import":"1","issue":"6","day":"21","quality_controlled":"1","project":[{"grant_number":"209504/A/17/Z","name":"Molecular mechanisms of neural circuit function","_id":"23870BE8-32DE-11EA-91FC-C7463DDC885E"}],"oa":1,"abstract":[{"text":"The ability to detect and respond to acute oxygen (O2) shortages is indispensable to aerobic life. The molecular mechanisms and circuits underlying this capacity are poorly understood. Here, we characterize the behavioral responses of feeding Caenorhabditis elegans to approximately 1% O2. Acute hypoxia triggers a bout of turning maneuvers followed by a persistent switch to rapid forward movement as animals seek to avoid and escape hypoxia. While the behavioral responses to 1% O2 closely resemble those evoked by 21% O2, they have distinct molecular and circuit underpinnings. Disrupting phosphodiesterases (PDEs), specific G proteins, or BBSome function inhibits escape from 1% O2 due to increased cGMP signaling. A primary source of cGMP is GCY-28, the ortholog of the atrial natriuretic peptide (ANP) receptor. cGMP activates the protein kinase G EGL-4 and enhances neuroendocrine secretion to inhibit acute responses to 1% O2. Triggering a rise in cGMP optogenetically in multiple neurons, including AIA interneurons, rapidly and reversibly inhibits escape from 1% O2. Ca2+ imaging reveals that a 7% to 1% O2 stimulus evokes a Ca2+ decrease in several neurons. Defects in mitochondrial complex I (MCI) and mitochondrial complex I (MCIII), which lead to persistently high reactive oxygen species (ROS), abrogate acute hypoxia responses. In particular, repressing the expression of isp-1, which encodes the iron sulfur protein of MCIII, inhibits escape from 1% O2 without affecting responses to 21% O2. Both genetic and pharmacological up-regulation of mitochondrial ROS increase cGMP levels, which contribute to the reduced hypoxia responses. Our results implicate ROS and precise regulation of intracellular cGMP in the modulation of acute responses to hypoxia by C. elegans.","lang":"eng"}],"date_created":"2022-07-24T22:01:42Z","fulldoi":"https://doi.org/10.1371/journal.pbio.3001684","acknowledgement":" This work was funded by H2020 European Research Council (ERC Advanced grant, 269058 ACMO, https://erc.europa.eu/funding/advanced-grants) and Wellcome Trust UK (Wellcome Investigator Award, 209504/Z/17/Z, https://wellcome.org/grant-funding/people-and-projects/grants-awarded/molecular-mechanisms-neural-circuit-function-0) to M.d.B, and by H2020 European Research Council (ERC starting grant, 802653 OXYGEN SENSING, https://erc.europa.eu/funding/starting-grants) and Vetenskapsrådet (VR starting grant, 2018-02216, https://www.vr.se/english.html) to C.C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","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)"},"article_number":"e3001684","type":"journal_article","volume":20,"publication_status":"published","file_date_updated":"2022-07-25T07:38:49Z","pmid":1,"language":[{"iso":"eng"}],"citation":{"chicago":"Zhao, Lina, Lorenz A. Fenk, Lars Nilsson, Niko Paresh Amin-Wetzel, Nelson Ramirez, Mario de Bono, and Changchun Chen. “ROS and CGMP Signaling Modulate Persistent Escape from Hypoxia in Caenorhabditis Elegans.” <i>PLoS Biology</i>. Public Library of Science, 2022. <a href=\"https://doi.org/10.1371/journal.pbio.3001684\">https://doi.org/10.1371/journal.pbio.3001684</a>.","ama":"Zhao L, Fenk LA, Nilsson L, et al. ROS and cGMP signaling modulate persistent escape from hypoxia in Caenorhabditis elegans. <i>PLoS Biology</i>. 2022;20(6). doi:<a href=\"https://doi.org/10.1371/journal.pbio.3001684\">10.1371/journal.pbio.3001684</a>","ista":"Zhao L, Fenk LA, Nilsson L, Amin-Wetzel NP, Ramirez N, de Bono M, Chen C. 2022. ROS and cGMP signaling modulate persistent escape from hypoxia in Caenorhabditis elegans. PLoS Biology. 20(6), e3001684.","mla":"Zhao, Lina, et al. “ROS and CGMP Signaling Modulate Persistent Escape from Hypoxia in Caenorhabditis Elegans.” <i>PLoS Biology</i>, vol. 20, no. 6, e3001684, Public Library of Science, 2022, doi:<a href=\"https://doi.org/10.1371/journal.pbio.3001684\">10.1371/journal.pbio.3001684</a>.","apa":"Zhao, L., Fenk, L. A., Nilsson, L., Amin-Wetzel, N. P., Ramirez, N., de Bono, M., &#38; Chen, C. (2022). ROS and cGMP signaling modulate persistent escape from hypoxia in Caenorhabditis elegans. <i>PLoS Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pbio.3001684\">https://doi.org/10.1371/journal.pbio.3001684</a>","ieee":"L. Zhao <i>et al.</i>, “ROS and cGMP signaling modulate persistent escape from hypoxia in Caenorhabditis elegans,” <i>PLoS Biology</i>, vol. 20, no. 6. Public Library of Science, 2022.","short":"L. Zhao, L.A. Fenk, L. Nilsson, N.P. Amin-Wetzel, N. Ramirez, M. de Bono, C. Chen, PLoS Biology 20 (2022)."},"isi":1,"article_type":"original","publication":"PLoS Biology","status":"public","author":[{"full_name":"Zhao, Lina","last_name":"Zhao","first_name":"Lina"},{"full_name":"Fenk, Lorenz A.","first_name":"Lorenz A.","last_name":"Fenk"},{"full_name":"Nilsson, Lars","last_name":"Nilsson","first_name":"Lars"},{"id":"E95D3014-9D8C-11E9-9C80-D2F8E5697425","full_name":"Amin-Wetzel, Niko Paresh","last_name":"Amin-Wetzel","first_name":"Niko Paresh"},{"id":"39831956-E4FE-11E9-85DE-0DC7E5697425","full_name":"Ramirez, Nelson","first_name":"Nelson","last_name":"Ramirez"},{"orcid":"0000-0001-8347-0443","full_name":"De Bono, Mario","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","last_name":"De Bono","first_name":"Mario"},{"last_name":"Chen","first_name":"Changchun","full_name":"Chen, Changchun"}],"date_updated":"2025-04-15T07:32:21Z","publisher":"Public Library of Science","has_accepted_license":"1","date_published":"2022-06-21T00:00:00Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"department":[{"_id":"MaDe"}],"oa_version":"Published Version","file":[{"file_size":3721585,"file_name":"2022_PLoSBiology_Zhao.pdf","relation":"main_file","checksum":"df4902f854ad76769d3203bfdc69f16c","creator":"dernst","date_updated":"2022-07-25T07:38:49Z","access_level":"open_access","success":1,"file_id":"11643","content_type":"application/pdf","date_created":"2022-07-25T07:38:49Z"}],"_id":"11637","external_id":{"pmid":["35727855"],"isi":["000828679600001"]},"doi":"10.1371/journal.pbio.3001684","month":"06","publication_identifier":{"eissn":["1545-7885"]},"article_processing_charge":"No","corr_author":"1","intvolume":"        20","year":"2022","title":"ROS and cGMP signaling modulate persistent escape from hypoxia in Caenorhabditis elegans"},{"_id":"12275","external_id":{"isi":["000797302700001"],"pmid":["35586945"]},"month":"07","doi":"10.15252/embr.202154163","publication_identifier":{"issn":["1469-221X"],"eissn":["1469-3178"]},"article_processing_charge":"No","intvolume":"        23","year":"2022","title":"Specific N-glycans regulate an extracellular adhesion complex during somatosensory dendrite patterning","citation":{"ista":"Rahman M, Ramirez N, Diaz‐Balzac CA, Bülow HE. 2022. Specific N-glycans regulate an extracellular adhesion complex during somatosensory dendrite patterning. EMBO Reports. 23(7), e54163.","ama":"Rahman M, Ramirez N, Diaz‐Balzac CA, Bülow HE. Specific N-glycans regulate an extracellular adhesion complex during somatosensory dendrite patterning. <i>EMBO Reports</i>. 2022;23(7). doi:<a href=\"https://doi.org/10.15252/embr.202154163\">10.15252/embr.202154163</a>","chicago":"Rahman, Maisha, Nelson Ramirez, Carlos A Diaz‐Balzac, and Hannes E Bülow. “Specific N-Glycans Regulate an Extracellular Adhesion Complex during Somatosensory Dendrite Patterning.” <i>EMBO Reports</i>. Embo Press, 2022. <a href=\"https://doi.org/10.15252/embr.202154163\">https://doi.org/10.15252/embr.202154163</a>.","short":"M. Rahman, N. Ramirez, C.A. Diaz‐Balzac, H.E. Bülow, EMBO Reports 23 (2022).","ieee":"M. Rahman, N. Ramirez, C. A. Diaz‐Balzac, and H. E. Bülow, “Specific N-glycans regulate an extracellular adhesion complex during somatosensory dendrite patterning,” <i>EMBO Reports</i>, vol. 23, no. 7. Embo Press, 2022.","apa":"Rahman, M., Ramirez, N., Diaz‐Balzac, C. A., &#38; Bülow, H. E. (2022). Specific N-glycans regulate an extracellular adhesion complex during somatosensory dendrite patterning. <i>EMBO Reports</i>. Embo Press. <a href=\"https://doi.org/10.15252/embr.202154163\">https://doi.org/10.15252/embr.202154163</a>","mla":"Rahman, Maisha, et al. “Specific N-Glycans Regulate an Extracellular Adhesion Complex during Somatosensory Dendrite Patterning.” <i>EMBO Reports</i>, vol. 23, no. 7, e54163, Embo Press, 2022, doi:<a href=\"https://doi.org/10.15252/embr.202154163\">10.15252/embr.202154163</a>."},"isi":1,"article_type":"original","publication":"EMBO Reports","status":"public","author":[{"last_name":"Rahman","first_name":"Maisha","full_name":"Rahman, Maisha"},{"first_name":"Nelson","last_name":"Ramirez","id":"39831956-E4FE-11E9-85DE-0DC7E5697425","full_name":"Ramirez, Nelson"},{"first_name":"Carlos A","last_name":"Diaz‐Balzac","full_name":"Diaz‐Balzac, Carlos A"},{"full_name":"Bülow, Hannes E","first_name":"Hannes E","last_name":"Bülow"}],"date_updated":"2026-06-18T17:26:25Z","publisher":"Embo Press","has_accepted_license":"1","date_published":"2022-07-05T00:00:00Z","keyword":["Genetics","Molecular Biology","Biochemistry"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"department":[{"_id":"MaDe"}],"oa_version":"Published Version","type":"journal_article","publication_status":"published","volume":23,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.15252/embr.202154163"}],"pmid":1,"language":[{"iso":"eng"}],"scopus_import":"1","issue":"7","day":"05","quality_controlled":"1","oa":1,"abstract":[{"text":"N-glycans are molecularly diverse sugars borne by over 70% of proteins transiting the secretory pathway and have been implicated in protein folding, stability, and localization. Mutations in genes important for N-glycosylation result in congenital disorders of glycosylation that are often associated with intellectual disability. Here, we show that structurally distinct N-glycans regulate an extracellular protein complex involved in the patterning of somatosensory dendrites in Caenorhabditis elegans. Specifically, aman-2/Golgi alpha-mannosidase II, a conserved key enzyme in the biosynthesis of specific N-glycans, regulates the activity of the Menorin adhesion complex without obviously affecting the protein stability and localization of its components. AMAN-2 functions cell-autonomously to allow for decoration of the neuronal transmembrane receptor DMA-1/LRR-TM with the correct set of high-mannose/hybrid/paucimannose N-glycans. Moreover, distinct types of N-glycans on specific N-glycosylation sites regulate DMA-1/LRR-TM receptor function, which, together with three other extracellular proteins, forms the Menorin adhesion complex. In summary, specific N-glycan structures regulate dendrite patterning by coordinating the activity of an extracellular adhesion complex, suggesting that the molecular diversity of N-glycans can contribute to developmental specificity in the nervous system.","lang":"eng"}],"acknowledgement":"We thank Scott Garforth, Sarah Garrett, Peri Kurshan, Yehuda Salzberg, PamelaStanley, Robert Townley, and members of the B€ulow laboratory for commentson the manuscript or helpful discussions during the course of this work. Wethank David Miller, Shohei Mitani, Kang Shen, and Iain Wilson for reagents,and Yuji Kohara for theyk11g705cDNA clone. We are grateful to MeeraTrivedi for sharing thedzIs117strain prior to publication. Some strains wereprovided by the Caenorhabditis Genome Center (funded by the NIH Office ofResearch Infrastructure Programs P40OD010440). This work was supportedby grants from the National Institute of Health (NIH): R01NS096672andR21NS111145to HEB; F31NS100370to MR; T32GM007288and F31HD066967to CADB; P30HD071593to Albert Einstein College of Medicine. We acknowl-edge support to MR by the Department of Neuroscience. NJRS was the recipi-ent of a Colciencias-Fulbright Fellowship and HEB of an Irma T. Hirschl/Monique Weill-Caulier research fellowship","fulldoi":"https://doi.org/10.15252/embr.202154163","date_created":"2023-01-16T10:01:44Z","article_number":"e54163"},{"status":"public","publisher":"Public Library of Science","date_updated":"2024-04-10T08:57:16Z","author":[{"full_name":"Tang, Leo T. H.","first_name":"Leo T. H.","last_name":"Tang"},{"full_name":"Trivedi, Meera","first_name":"Meera","last_name":"Trivedi"},{"last_name":"Freund","first_name":"Jenna","full_name":"Freund, Jenna"},{"full_name":"Salazar, Christopher J.","first_name":"Christopher J.","last_name":"Salazar"},{"first_name":"Maisha","last_name":"Rahman","full_name":"Rahman, Maisha"},{"id":"39831956-E4FE-11E9-85DE-0DC7E5697425","full_name":"Ramirez, Nelson","first_name":"Nelson","last_name":"Ramirez"},{"full_name":"Lee, Garrett","first_name":"Garrett","last_name":"Lee"},{"full_name":"Wang, Yu","last_name":"Wang","first_name":"Yu"},{"full_name":"Grant, Barth D.","last_name":"Grant","first_name":"Barth D."},{"first_name":"Hannes E.","last_name":"Bülow","full_name":"Bülow, Hannes E."}],"citation":{"ama":"Tang LTH, Trivedi M, Freund J, et al. The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning. <i>PLOS Genetics</i>. 2021;17(7). doi:<a href=\"https://doi.org/10.1371/journal.pgen.1009475\">10.1371/journal.pgen.1009475</a>","ista":"Tang LTH, Trivedi M, Freund J, Salazar CJ, Rahman M, Ramirez N, Lee G, Wang Y, Grant BD, Bülow HE. 2021. The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning. PLOS Genetics. 17(7), e1009475.","chicago":"Tang, Leo T. H., Meera Trivedi, Jenna Freund, Christopher J. Salazar, Maisha Rahman, Nelson Ramirez, Garrett Lee, Yu Wang, Barth D. Grant, and Hannes E. Bülow. “The CATP-8/P5A-Type ATPase Functions in Multiple Pathways during Neuronal Patterning.” <i>PLOS Genetics</i>. Public Library of Science, 2021. <a href=\"https://doi.org/10.1371/journal.pgen.1009475\">https://doi.org/10.1371/journal.pgen.1009475</a>.","short":"L.T.H. Tang, M. Trivedi, J. Freund, C.J. Salazar, M. Rahman, N. Ramirez, G. Lee, Y. Wang, B.D. Grant, H.E. Bülow, PLOS Genetics 17 (2021).","ieee":"L. T. H. Tang <i>et al.</i>, “The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning,” <i>PLOS Genetics</i>, vol. 17, no. 7. Public Library of Science, 2021.","apa":"Tang, L. T. H., Trivedi, M., Freund, J., Salazar, C. J., Rahman, M., Ramirez, N., … Bülow, H. E. (2021). The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning. <i>PLOS Genetics</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pgen.1009475\">https://doi.org/10.1371/journal.pgen.1009475</a>","mla":"Tang, Leo T. H., et al. “The CATP-8/P5A-Type ATPase Functions in Multiple Pathways during Neuronal Patterning.” <i>PLOS Genetics</i>, vol. 17, no. 7, e1009475, Public Library of Science, 2021, doi:<a href=\"https://doi.org/10.1371/journal.pgen.1009475\">10.1371/journal.pgen.1009475</a>."},"publication":"PLOS Genetics","article_type":"original","file":[{"date_created":"2024-04-10T08:53:43Z","file_id":"15308","content_type":"application/pdf","success":1,"access_level":"open_access","creator":"dernst","checksum":"7352b195e4db6d404f702fe6ad8b55ad","date_updated":"2024-04-10T08:53:43Z","relation":"main_file","file_name":"2021_PlosGenetics_Tang.pdf","file_size":4224934}],"oa_version":"Published Version","date_published":"2021-07-01T00:00:00Z","keyword":["Cancer Research","Genetics (clinical)","Genetics","Molecular Biology","Ecology","Evolution","Behavior and Systematics"],"has_accepted_license":"1","department":[{"_id":"MaDe"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"month":"07","doi":"10.1371/journal.pgen.1009475","article_processing_charge":"No","publication_identifier":{"issn":["1553-7404"]},"external_id":{"pmid":["34197450"]},"_id":"15272","title":"The CATP-8/P5A-type ATPase functions in multiple pathways during neuronal patterning","year":"2021","intvolume":"        17","quality_controlled":"1","issue":"7","day":"01","date_created":"2024-04-03T07:57:12Z","fulldoi":"https://doi.org/10.1371/journal.pgen.1009475","article_number":"e1009475","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)"},"oa":1,"abstract":[{"lang":"eng","text":"The assembly of neuronal circuits involves the migrations of neurons from their place of birth to their final location in the nervous system, as well as the coordinated growth and patterning of axons and dendrites. In screens for genes required for patterning of the nervous system, we identified the <jats:italic>catp-8/P5A-ATPase</jats:italic> as an important regulator of neural patterning. P5A-ATPases are part of the P-type ATPases, a family of proteins known to serve a conserved function as transporters of ions, lipids and polyamines in unicellular eukaryotes, plants, and humans. While the function of many P-type ATPases is relatively well understood, the function of P5A-ATPases in metazoans remained elusive. We show here, that the <jats:italic>Caenorhabditis elegans</jats:italic> ortholog <jats:italic>catp-8/P5A-ATPase</jats:italic> is required for defined aspects of nervous system development. Specifically, the <jats:italic>catp-8/P5A-ATPase</jats:italic> serves functions in shaping the elaborately sculpted dendritic trees of somatosensory PVD neurons. Moreover, <jats:italic>catp-8/P5A-ATPase</jats:italic> is required for axonal guidance and repulsion at the midline, as well as embryonic and postembryonic neuronal migrations. Interestingly, not all axons at the midline require <jats:italic>catp-8/P5A-ATPase</jats:italic>, although the axons run in the same fascicles and navigate the same space. Similarly, not all neuronal migrations require <jats:italic>catp-8/P5A-ATPase</jats:italic>. A CATP-8/P5A-ATPase reporter is localized to the ER in most, if not all, tissues and <jats:italic>catp-8/P5A-ATPase</jats:italic> can function both cell-autonomously and non-autonomously to regulate neuronal development. Genetic analyses establish that <jats:italic>catp-8/P5A-ATPase</jats:italic> can function in multiple pathways, including the Menorin pathway, previously shown to control dendritic patterning in PVD, and Wnt signaling, which functions to control neuronal migrations. Lastly, we show that <jats:italic>catp-8/P5A-ATPase</jats:italic> is required for localizing select transmembrane proteins necessary for dendrite morphogenesis. Collectively, our studies suggest that <jats:italic>catp-8/P5A-ATPase</jats:italic> serves diverse, yet specific, roles in different genetic pathways and may be involved in the regulation or localization of transmembrane and secreted proteins to specific subcellular compartments."}],"file_date_updated":"2024-04-10T08:53:43Z","type":"journal_article","publication_status":"published","volume":17,"language":[{"iso":"eng"}],"pmid":1}]