[{"intvolume":"        16","article_number":"11355","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"year":"2025","OA_place":"publisher","date_published":"2025-12-11T00:00:00Z","external_id":{"pmid":["41381452"]},"abstract":[{"lang":"eng","text":"Insulin/insulin-like growth factor signaling inhibits FOXO transcription factors to control development, homeostasis, and aging. Here, we use proximity labeling to identify proteins interacting with the C. elegans FOXO DAF-16. We show that in well-fed, unstressed animals harboring active insulin signaling, DAF-16 forms a complex with the PAR-1/MARK serine/threonine kinase, a key regulator of cell polarity. PAR-1 inhibits DAF-16 accumulation and promotes DAF-16 phosphorylation at S249, at a conserved motif that PAR-1/human MARK2 phosphorylates in vitro. DAF-2 insulin-like receptor signaling stimulates DAF-16 S249 phosphorylation, suggesting DAF-2 activates PAR-1. DAF-2 also promotes PAR-1 expression by inhibiting DAF-16. PAR-1 knockdown, or DAF-16 S249A, prolong lifespan, whereas phosphomimetic DAF-16 S249D suppresses the longevity of daf-2 mutants. At low insulin signaling, DAF-16 proximity labeling highlights transcription factors, chromatin regulators, and DNA repair proteins. One interactor, the zinc finger/homeobox protein ZFH-2/ZFHX3, forms a complex with DAF-16 and prolongs lifespan. Our work provides entry points for hypothesis-driven studies of FOXO function and longevity."}],"_id":"20929","language":[{"iso":"eng"}],"quality_controlled":"1","type":"journal_article","day":"11","citation":{"apa":"Artan, M., Schön, H., &#38; de Bono, M. (2025). Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-025-66409-0\">https://doi.org/10.1038/s41467-025-66409-0</a>","mla":"Artan, Murat, et al. “Proximity Labeling of DAF-16 FOXO Highlights Aging Regulatory Proteins.” <i>Nature Communications</i>, vol. 16, 11355, Springer Nature, 2025, doi:<a href=\"https://doi.org/10.1038/s41467-025-66409-0\">10.1038/s41467-025-66409-0</a>.","ieee":"M. Artan, H. Schön, and M. de Bono, “Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins,” <i>Nature Communications</i>, vol. 16. Springer Nature, 2025.","short":"M. Artan, H. Schön, M. de Bono, Nature Communications 16 (2025).","chicago":"Artan, Murat, Hanna Schön, and Mario de Bono. “Proximity Labeling of DAF-16 FOXO Highlights Aging Regulatory Proteins.” <i>Nature Communications</i>. Springer Nature, 2025. <a href=\"https://doi.org/10.1038/s41467-025-66409-0\">https://doi.org/10.1038/s41467-025-66409-0</a>.","ama":"Artan M, Schön H, de Bono M. Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins. <i>Nature Communications</i>. 2025;16. doi:<a href=\"https://doi.org/10.1038/s41467-025-66409-0\">10.1038/s41467-025-66409-0</a>","ista":"Artan M, Schön H, de Bono M. 2025. Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins. Nature Communications. 16, 11355."},"has_accepted_license":"1","PlanS_conform":"1","status":"public","license":"https://creativecommons.org/licenses/by/4.0/","ec_funded":1,"DOAJ_listed":"1","scopus_import":"1","file_date_updated":"2026-01-05T10:58:28Z","date_updated":"2026-01-05T11:00:03Z","publication":"Nature Communications","acknowledged_ssus":[{"_id":"Bio"}],"publication_identifier":{"eissn":["2041-1723"]},"date_created":"2026-01-04T23:01:34Z","title":"Proximity labeling of DAF-16 FOXO highlights aging regulatory proteins","OA_type":"gold","oa_version":"Published Version","publication_status":"published","file":[{"success":1,"content_type":"application/pdf","date_created":"2026-01-05T10:58:28Z","file_size":1642352,"access_level":"open_access","creator":"dernst","file_id":"20941","date_updated":"2026-01-05T10:58:28Z","relation":"main_file","checksum":"748e2e003b878b85b6048d51621d6aae","file_name":"2025_NatureComm_Artan.pdf"}],"article_processing_charge":"Yes","corr_author":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"publisher":"Springer Nature","pmid":1,"doi":"10.1038/s41467-025-66409-0","oa":1,"acknowledgement":"We thank de Bono lab members for helpful comments on the manuscript, and the Mass Spec Facility at the Max Perutz Labs, notably WeiQiang Chen and Markus Hartl, for invaluable discussions and comments on mass spec analyses of worm samples. All LC-MS/MS analyses were performed on instruments of the Vienna BioCenter Core Facilities (VBCF). Microscopy was supported by the Scientific Services Units (SSU) of ISTA through resources provided by the Imaging & Optics Facility (IOF). We are grateful to Dr. Geraldine Seydoux (Johns Hopkins University) for worm strains and plasmids, and Dr. Seung-Jae V. Lee (KAIST) for RNAi clones. We are grateful to Ekaterina Lashmanova for designing the daf-16::TbID::mNG::3xFLAG knock-in construct and for her outstanding support in the lab. This work was supported by a Wellcome Investigator Award (209504/A/17/Z) to MdB and an ISTplus Fellowship to MA (Marie Sklodowska-Curie agreement No 754411).","volume":16,"author":[{"last_name":"Artan","full_name":"Artan, Murat","first_name":"Murat","id":"C407B586-6052-11E9-B3AE-7006E6697425","orcid":"0000-0001-8945-6992"},{"first_name":"Hanna","id":"C8E17EDC-D7AA-11E9-B7B7-45ECE5697425","last_name":"Schön","full_name":"Schön, Hanna"},{"full_name":"De Bono, Mario","last_name":"De Bono","first_name":"Mario","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8347-0443"}],"department":[{"_id":"MaDe"}],"month":"12","project":[{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"},{"grant_number":"209504/A/17/Z","_id":"23870BE8-32DE-11EA-91FC-C7463DDC885E","name":"Molecular mechanisms of neural circuit function"}],"article_type":"original"},{"tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"corr_author":"1","article_processing_charge":"No","publisher":"Institute of Science and Technology Austria","degree_awarded":"PhD","acknowledgement":"This work was supported by EMBO (ALTF 302-2019 to Niko Amin-Wetzel), the FWF\r\n(ESPRIT PR1054E140 to Niko Amin-Wetzel), the European Research Council\r\n(Advanced Grant 269058 to Mario de Bono) and Wellcome (209504/A/17/Z\r\nInvestigator Award to Mario de Bono). ","doi":"10.15479/AT-ISTA-20167","author":[{"full_name":"Schön, Hanna","last_name":"Schön","id":"C8E17EDC-D7AA-11E9-B7B7-45ECE5697425","first_name":"Hanna"}],"project":[{"_id":"23870BE8-32DE-11EA-91FC-C7463DDC885E","grant_number":"209504/A/17/Z","name":"Molecular mechanisms of neural circuit function"},{"name":"Control of gene expression at the endoplasmic reticulum","grant_number":"ALTF 302-2019","_id":"23813290-32DE-11EA-91FC-C7463DDC885E"}],"department":[{"_id":"GradSch"},{"_id":"MaDe"}],"month":"08","publication_identifier":{"isbn":["978-3-99078-061-9"],"issn":["2663-337X"]},"title":"The ER complex SUTU-7/MACO-1 regulates the fate of mRNAs encoding GPCRs","alternative_title":["ISTA Thesis"],"date_created":"2025-08-13T11:13:13Z","oa_version":"Published Version","supervisor":[{"id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","first_name":"Mario","orcid":"0000-0001-8347-0443","last_name":"de Bono","full_name":"de Bono, Mario"}],"publication_status":"published","file":[{"file_size":78812587,"date_created":"2025-09-08T14:33:50Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","access_level":"closed","date_updated":"2025-09-09T08:57:04Z","file_id":"20311","relation":"source_file","creator":"hschoen","file_name":"2025_Schoen_Hanna_Thesis.docx","checksum":"b40c74404b8d9593802dabf57bfdf10f"},{"embargo_to":"open_access","date_created":"2025-09-11T14:20:59Z","file_size":9667057,"content_type":"application/pdf","access_level":"closed","embargo":"2026-09-15","date_updated":"2025-09-18T14:12:29Z","creator":"hschoen","file_id":"20347","relation":"main_file","file_name":"2025_Schoen_Hanna_Thesis.pdf","checksum":"16abc3ff66396ce2457fe07ffa8bed90"}],"status":"public","page":"171","file_date_updated":"2025-09-18T14:12:29Z","date_updated":"2026-04-07T11:50:26Z","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"year":"2025","ddc":["570"],"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","date_published":"2025-08-13T00:00:00Z","OA_place":"publisher","language":[{"iso":"eng"}],"_id":"20167","type":"dissertation","has_accepted_license":"1","citation":{"apa":"Schön, H. (2025). <i>The ER complex SUTU-7/MACO-1 regulates the fate of mRNAs encoding GPCRs</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT-ISTA-20167\">https://doi.org/10.15479/AT-ISTA-20167</a>","mla":"Schön, Hanna. <i>The ER Complex SUTU-7/MACO-1 Regulates the Fate of MRNAs Encoding GPCRs</i>. Institute of Science and Technology Austria, 2025, doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20167\">10.15479/AT-ISTA-20167</a>.","ieee":"H. Schön, “The ER complex SUTU-7/MACO-1 regulates the fate of mRNAs encoding GPCRs,” Institute of Science and Technology Austria, 2025.","short":"H. Schön, The ER Complex SUTU-7/MACO-1 Regulates the Fate of MRNAs Encoding GPCRs, Institute of Science and Technology Austria, 2025.","chicago":"Schön, Hanna. “The ER Complex SUTU-7/MACO-1 Regulates the Fate of MRNAs Encoding GPCRs.” Institute of Science and Technology Austria, 2025. <a href=\"https://doi.org/10.15479/AT-ISTA-20167\">https://doi.org/10.15479/AT-ISTA-20167</a>.","ama":"Schön H. The ER complex SUTU-7/MACO-1 regulates the fate of mRNAs encoding GPCRs. 2025. doi:<a href=\"https://doi.org/10.15479/AT-ISTA-20167\">10.15479/AT-ISTA-20167</a>","ista":"Schön H. 2025. The ER complex SUTU-7/MACO-1 regulates the fate of mRNAs encoding GPCRs. Institute of Science and Technology Austria."},"day":"13"},{"date_created":"2022-06-20T08:10:34Z","title":"Proteomic Analysis of C. Elegans Neurons Using TurboID-Based Proximity Labeling","alternative_title":["Neuromethods"],"oa_version":"None","place":"New York","publication_identifier":{"isbn":["9781071623206"],"eisbn":["9781071623213"],"eissn":["1940-6045"],"issn":["0893-2336"]},"publication_status":"published","series_title":"NM","article_processing_charge":"No","corr_author":"1","publisher":"Springer Nature","author":[{"orcid":"0000-0001-8945-6992","id":"C407B586-6052-11E9-B3AE-7006E6697425","first_name":"Murat","full_name":"Artan, Murat","last_name":"Artan"},{"first_name":"Mario","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8347-0443","last_name":"de Bono","full_name":"de Bono, Mario"}],"volume":181,"month":"06","department":[{"_id":"MaDe"}],"project":[{"grant_number":"209504/A/17/Z","_id":"23870BE8-32DE-11EA-91FC-C7463DDC885E","name":"Molecular mechanisms of neural circuit function"},{"name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425"}],"doi":"10.1007/978-1-0716-2321-3_15","acknowledgement":"We thank de Bono lab members for the helpful comments on the manuscript. The biotin-auxotrophic E. coli strain MG1655bioB:kan was a generous gift from J. 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 sent by Dr. Dominique Glauser (University of Fribourg). This work was supported by an Advanced ERC Grant (269058 ACMO) and a Wellcome Investigator Award (209504/Z/17/Z) to MdB and an ISTplus Fellowship to MA (Marie Sklodowska-Curie agreement No 754411).","date_published":"2022-06-04T00:00:00Z","intvolume":"       181","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2022","day":"04","citation":{"mla":"Artan, Murat, and Mario de Bono. “Proteomic Analysis of C. Elegans Neurons Using TurboID-Based Proximity Labeling.” <i>Behavioral Neurogenetics</i>, edited by Daisuke Yamamoto, vol. 181, Springer Nature, 2022, pp. 277–94, doi:<a href=\"https://doi.org/10.1007/978-1-0716-2321-3_15\">10.1007/978-1-0716-2321-3_15</a>.","short":"M. Artan, M. de Bono, in:, D. Yamamoto (Ed.), Behavioral Neurogenetics, Springer Nature, New York, 2022, pp. 277–294.","ieee":"M. Artan and M. de Bono, “Proteomic Analysis of C. Elegans Neurons Using TurboID-Based Proximity Labeling,” in <i>Behavioral Neurogenetics</i>, vol. 181, D. Yamamoto, Ed. New York: Springer Nature, 2022, pp. 277–294.","apa":"Artan, M., &#38; de Bono, M. (2022). Proteomic Analysis of C. Elegans Neurons Using TurboID-Based Proximity Labeling. In D. Yamamoto (Ed.), <i>Behavioral Neurogenetics</i> (Vol. 181, pp. 277–294). New York: Springer Nature. <a href=\"https://doi.org/10.1007/978-1-0716-2321-3_15\">https://doi.org/10.1007/978-1-0716-2321-3_15</a>","ama":"Artan M, de Bono M. Proteomic Analysis of C. Elegans Neurons Using TurboID-Based Proximity Labeling. In: Yamamoto D, ed. <i>Behavioral Neurogenetics</i>. Vol 181. NM. New York: Springer Nature; 2022:277-294. doi:<a href=\"https://doi.org/10.1007/978-1-0716-2321-3_15\">10.1007/978-1-0716-2321-3_15</a>","ista":"Artan M, de Bono M. 2022.Proteomic Analysis of C. Elegans Neurons Using TurboID-Based Proximity Labeling. In: Behavioral Neurogenetics. Neuromethods, vol. 181, 277–294.","chicago":"Artan, Murat, and Mario de Bono. “Proteomic Analysis of C. Elegans Neurons Using TurboID-Based Proximity Labeling.” In <i>Behavioral Neurogenetics</i>, edited by Daisuke Yamamoto, 181:277–94. NM. New York: Springer Nature, 2022. <a href=\"https://doi.org/10.1007/978-1-0716-2321-3_15\">https://doi.org/10.1007/978-1-0716-2321-3_15</a>."},"abstract":[{"text":"The proteomes of specialized structures, and the interactomes of proteins of interest, provide entry points to elucidate the functions of molecular machines. Here, we review a proximity-labeling strategy that uses the improved E. coli biotin ligase TurboID to characterize C. elegans protein complexes. Although the focus is on C. elegans neurons, the method is applicable regardless of cell type. We describe detailed extraction procedures that solubilize the bulk of C. elegans proteins and highlight the importance of tagging endogenous genes, to ensure physiological expression levels. We review issues associated with non-specific background noise and the importance of appropriate controls. As proof of principle, we review our analysis of the interactome of a presynaptic active zone protein, ELKS-1. Our aim is to provide a detailed protocol for TurboID-based proximity labeling in C. elegans and to highlight its potential and its limitations to characterize protein complexes and subcellular compartments in this animal.","lang":"eng"}],"_id":"11456","language":[{"iso":"eng"}],"quality_controlled":"1","type":"book_chapter","ec_funded":1,"editor":[{"first_name":"Daisuke","full_name":"Yamamoto, Daisuke","last_name":"Yamamoto"}],"scopus_import":"1","status":"public","page":"277-294","publication":"Behavioral Neurogenetics","date_updated":"2025-04-14T07:43:58Z"},{"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.","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>","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>.","short":"L. Zhao, L.A. Fenk, L. Nilsson, N.P. Amin-Wetzel, N. Ramirez, M. de Bono, C. Chen, PLoS Biology 20 (2022).","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."},"day":"21","has_accepted_license":"1","quality_controlled":"1","type":"journal_article","external_id":{"pmid":["35727855"],"isi":["000828679600001"]},"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"}],"_id":"11637","language":[{"iso":"eng"}],"date_published":"2022-06-21T00:00:00Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"year":"2022","article_number":"e3001684","intvolume":"        20","isi":1,"publication":"PLoS Biology","date_updated":"2025-04-15T07:32:21Z","file_date_updated":"2022-07-25T07:38:49Z","scopus_import":"1","issue":"6","status":"public","file":[{"content_type":"application/pdf","success":1,"file_size":3721585,"date_created":"2022-07-25T07:38:49Z","access_level":"open_access","file_id":"11643","relation":"main_file","date_updated":"2022-07-25T07:38:49Z","creator":"dernst","checksum":"df4902f854ad76769d3203bfdc69f16c","file_name":"2022_PLoSBiology_Zhao.pdf"}],"publication_status":"published","oa_version":"Published Version","title":"ROS and cGMP signaling modulate persistent escape from hypoxia in Caenorhabditis elegans","date_created":"2022-07-24T22:01:42Z","publication_identifier":{"eissn":["1545-7885"]},"department":[{"_id":"MaDe"}],"month":"06","article_type":"original","project":[{"name":"Molecular mechanisms of neural circuit function","_id":"23870BE8-32DE-11EA-91FC-C7463DDC885E","grant_number":"209504/A/17/Z"}],"author":[{"first_name":"Lina","full_name":"Zhao, Lina","last_name":"Zhao"},{"first_name":"Lorenz A.","last_name":"Fenk","full_name":"Fenk, Lorenz A."},{"first_name":"Lars","full_name":"Nilsson, Lars","last_name":"Nilsson"},{"full_name":"Amin-Wetzel, Niko Paresh","last_name":"Amin-Wetzel","first_name":"Niko Paresh","id":"E95D3014-9D8C-11E9-9C80-D2F8E5697425"},{"full_name":"Ramirez, Nelson","last_name":"Ramirez","id":"39831956-E4FE-11E9-85DE-0DC7E5697425","first_name":"Nelson"},{"last_name":"De Bono","full_name":"De Bono, Mario","first_name":"Mario","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8347-0443"},{"first_name":"Changchun","full_name":"Chen, Changchun","last_name":"Chen"}],"volume":20,"doi":"10.1371/journal.pbio.3001684","oa":1,"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.","pmid":1,"publisher":"Public Library of Science","article_processing_charge":"No","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"corr_author":"1"},{"publication_status":"published","file":[{"file_name":"2022_JBC_Artan.pdf","checksum":"e726c7b9315230e6710e0b1f1d1677e9","creator":"dernst","date_updated":"2022-09-12T08:14:50Z","file_id":"12092","relation":"main_file","access_level":"open_access","date_created":"2022-09-12T08:14:50Z","file_size":2101656,"success":1,"content_type":"application/pdf"}],"publication_identifier":{"issn":["0021-9258"],"eissn":["1083-351X"]},"date_created":"2022-09-11T22:01:55Z","title":"Depletion of endogenously biotinylated carboxylases enhances the sensitivity of TurboID-mediated proximity labeling in Caenorhabditis elegans","oa_version":"Published Version","doi":"10.1016/j.jbc.2022.102343","oa":1,"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).","author":[{"full_name":"Artan, Murat","last_name":"Artan","first_name":"Murat","id":"C407B586-6052-11E9-B3AE-7006E6697425","orcid":"0000-0001-8945-6992"},{"first_name":"Markus","full_name":"Hartl, Markus","last_name":"Hartl"},{"first_name":"Weiqiang","full_name":"Chen, Weiqiang","last_name":"Chen"},{"orcid":"0000-0001-8347-0443","first_name":"Mario","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","last_name":"De Bono","full_name":"De Bono, Mario"}],"volume":298,"department":[{"_id":"MaDe"}],"month":"09","article_type":"original","project":[{"name":"Molecular mechanisms of neural circuit function","_id":"23870BE8-32DE-11EA-91FC-C7463DDC885E","grant_number":"209504/A/17/Z"},{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships"}],"article_processing_charge":"No","corr_author":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"publisher":"Elsevier","pmid":1,"external_id":{"pmid":["35933017"],"isi":["000884241800011"]},"_id":"12082","language":[{"iso":"eng"}],"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."}],"quality_controlled":"1","type":"journal_article","citation":{"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>.","short":"M. Artan, M. Hartl, W. Chen, M. de Bono, Journal of Biological Chemistry 298 (2022).","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.","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>","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>","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.","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>."},"day":"01","has_accepted_license":"1","intvolume":"       298","article_number":"102343","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"year":"2022","date_published":"2022-09-01T00:00:00Z","file_date_updated":"2022-09-12T08:14:50Z","date_updated":"2025-04-14T07:44:00Z","publication":"Journal of Biological Chemistry","isi":1,"acknowledged_ssus":[{"_id":"Bio"}],"status":"public","ec_funded":1,"issue":"9","scopus_import":"1"},{"scopus_import":"1","status":"public","isi":1,"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"ScienComp"}],"publication":"eLife","date_updated":"2026-04-02T12:45:39Z","file_date_updated":"2022-03-07T07:39:25Z","date_published":"2022-02-24T00:00:00Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","ddc":["570"],"year":"2022","article_number":"e68040","intvolume":"        11","citation":{"apa":"Valperga, G., &#38; de Bono, M. (2022). Impairing one sensory modality enhances another by reconfiguring peptidergic signalling in Caenorhabditis elegans. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.68040\">https://doi.org/10.7554/eLife.68040</a>","ieee":"G. Valperga and M. de Bono, “Impairing one sensory modality enhances another by reconfiguring peptidergic signalling in Caenorhabditis elegans,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","short":"G. Valperga, M. de Bono, ELife 11 (2022).","mla":"Valperga, Giulio, and Mario de Bono. “Impairing One Sensory Modality Enhances Another by Reconfiguring Peptidergic Signalling in Caenorhabditis Elegans.” <i>ELife</i>, vol. 11, e68040, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/eLife.68040\">10.7554/eLife.68040</a>.","chicago":"Valperga, Giulio, and Mario de Bono. “Impairing One Sensory Modality Enhances Another by Reconfiguring Peptidergic Signalling in Caenorhabditis Elegans.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/eLife.68040\">https://doi.org/10.7554/eLife.68040</a>.","ista":"Valperga G, de Bono M. 2022. Impairing one sensory modality enhances another by reconfiguring peptidergic signalling in Caenorhabditis elegans. eLife. 11, e68040.","ama":"Valperga G, de Bono M. Impairing one sensory modality enhances another by reconfiguring peptidergic signalling in Caenorhabditis elegans. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/eLife.68040\">10.7554/eLife.68040</a>"},"day":"24","has_accepted_license":"1","quality_controlled":"1","type":"journal_article","external_id":{"isi":["000763432300001"],"pmid":["35201977"]},"abstract":[{"lang":"eng","text":"Animals that lose one sensory modality often show augmented responses to other sensory inputs. The mechanisms underpinning this cross-modal plasticity are poorly understood. We probe such mechanisms by performing a forward genetic screen for mutants with enhanced O2 perception in Caenorhabditis elegans. Multiple mutants exhibiting increased O2 responsiveness concomitantly show defects in other sensory responses. One mutant, qui-1, defective in a conserved NACHT/WD40 protein, abolishes pheromone-evoked Ca2+ responses in the ADL pheromone-sensing neurons. At the same time, ADL responsiveness to pre-synaptic input from O2-sensing neurons is heightened in qui-1, and other sensory defective mutants, resulting in enhanced neurosecretion although not increased Ca2+ responses. Expressing qui-1 selectively in ADL rescues both the qui-1 ADL neurosecretory phenotype and enhanced escape from 21% O2. Profiling ADL neurons in qui-1 mutants highlights extensive changes in gene expression, notably of many neuropeptide receptors. We show that elevated ADL expression of the conserved neuropeptide receptor NPR-22 is necessary for enhanced ADL neurosecretion in qui-1 mutants, and is sufficient to confer increased ADL neurosecretion in control animals. Sensory loss can thus confer cross-modal plasticity by changing the peptidergic connectome."}],"_id":"10826","language":[{"iso":"eng"}],"pmid":1,"publisher":"eLife Sciences Publications","article_processing_charge":"No","corr_author":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"department":[{"_id":"MaDe"}],"month":"02","article_type":"original","project":[{"name":"Molecular mechanisms of neural circuit function","_id":"23870BE8-32DE-11EA-91FC-C7463DDC885E","grant_number":"209504/A/17/Z"}],"volume":11,"author":[{"orcid":"0000-0001-6726-3890","first_name":"Giulio","id":"67F289DE-0D8F-11EA-9BDD-54AE3DDC885E","full_name":"Valperga, Giulio","last_name":"Valperga"},{"full_name":"De Bono, Mario","last_name":"De Bono","first_name":"Mario","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8347-0443"}],"oa":1,"doi":"10.7554/eLife.68040","acknowledgement":"We would like to thank Gemma Chandratillake and Merav Cohen for identifying mutants and José David Moñino Sánchez for his help on neurosecretion assays. We are grateful to Kaveh Ashrafi (UCSF), Piali Sengupta (Brandeis), and the Caenorhabditis Genetic Center (funded by National Institutes of Health Infrastructure Program P40 OD010440) for strains and reagents ... and Rebecca Butcher (Univ. Florida) for C9 pheromone. We thank Tim Stevens, Paula Freire-Pritchett, Alastair Crisp, GurpreetGhattaoraya, and Fabian Amman for help with bioinformatic analysis, Ekaterina Lashmanova for help with injections, Iris Hardege for strains, and Isabel Beets (KU Leuven) and members of the de Bono Lab for comments on the manuscript. We thank the CRUK Cambridge Research Institute Genomics Core for next generation sequencing and the Flow Cytometry Facility at LMB for FACS. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility (BIF), the Life Science Facility (LSF) and Scientific Computing (SciCo-p– Bioinformatics).\r\nThis work was supported by the Medical Research Council UK (Studentship to GV), an\r\nAdvanced ERC grant (269,058 ACMO to MdB), and a Wellcome Investigator Award (209504/Z/17/Z to MdB).","oa_version":"Published Version","title":"Impairing one sensory modality enhances another by reconfiguring peptidergic signalling in Caenorhabditis elegans","date_created":"2022-03-06T23:01:52Z","publication_identifier":{"eissn":["2050-084X"]},"file":[{"date_created":"2022-03-07T07:39:25Z","file_size":4095591,"content_type":"application/pdf","success":1,"access_level":"open_access","file_id":"10830","date_updated":"2022-03-07T07:39:25Z","relation":"main_file","creator":"dernst","file_name":"2022_eLife_Valperga.pdf","checksum":"cc1b9bf866d0f61f965556e0dd03d3ac"}],"publication_status":"published"}]