{"doi":"10.1073/pnas.1203306109","title":"RAB-5 and RAB-10 cooperate to regulate neuropeptide release in\n                    <i>Caenorhabditis elegans</i>","abstract":"<jats:p>\n                    Neurons secrete neuropeptides from dense core vesicles (DCVs) to modulate neuronal activity. Little is known about how neurons manage to differentially regulate the release of synaptic vesicles (SVs) and DCVs. To analyze this, we screened all\n                    <jats:italic>Caenorhabditis elegans</jats:italic>\n                    Rab GTPases and Tre2/Bub2/Cdc16 (TBC) domain containing GTPase-activating proteins (GAPs) for defects in DCV release from\n                    <jats:italic>C. elegans</jats:italic>\n                    motoneurons.\n                    <jats:italic>rab</jats:italic>\n                    <jats:italic>-5</jats:italic>\n                    and\n                    <jats:italic>rab</jats:italic>\n                    <jats:italic>-10</jats:italic>\n                    mutants show severe defects in DCV secretion, whereas SV exocytosis is unaffected. We identified TBC-2 and TBC-4 as putative GAPs for RAB-5 and RAB-10, respectively. Multiple Rabs and RabGAPs are typically organized in cascades that confer directionality to membrane-trafficking processes. We show here that the formation of release-competent DCVs requires a reciprocal exclusion cascade coupling RAB-5 and RAB-10, in which each of the two Rabs recruits the other’s GAP molecule. This contributes to a separation of RAB-5 and RAB-10 domains at the Golgi–endosomal interface, which is lost when either of the two GAPs is inactivated. Taken together, our data suggest that RAB-5 and RAB-10 cooperate to locally exclude each other at an essential stage during DCV sorting.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2012,"id":619310,"datarank":0.62147020895873,"base_score":4.143134726391533,"endowment":4.143134726391533,"self_citation_contribution":0.62147020895873,"citation_network_contribution":0.0,"self_endowment_contribution":0.62147020895873,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":62,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1598165,"name":"Marija Sumakovic","orcid":null,"position":1,"is_corresponding":false},{"id":1598166,"name":"Mandy Hannemann","orcid":null,"position":2,"is_corresponding":false},{"id":277377,"name":"Jan Hegermann","orcid":"0000-0001-7893-8507","position":3,"is_corresponding":false},{"id":1598167,"name":"Jana F. Liewald","orcid":null,"position":4,"is_corresponding":false},{"id":1598168,"name":"Christian Olendrowitz","orcid":null,"position":5,"is_corresponding":false},{"id":1598169,"name":"Sabine Koenig","orcid":null,"position":6,"is_corresponding":false},{"id":304338,"name":"Barth D. Grant","orcid":"0000-0002-5943-8336","position":7,"is_corresponding":false},{"id":647722,"name":"Silvio O. Rizzoli","orcid":"0000-0002-1667-7839","position":8,"is_corresponding":false},{"id":349997,"name":"Alexander Gottschalk","orcid":"0000-0002-1197-6119","position":9,"is_corresponding":false},{"id":1057882,"name":"Stefan Eimer","orcid":null,"position":10,"is_corresponding":false},{"id":1598164,"name":"Nikhil Sasidharan","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"RAB-5 and RAB-10 cooperate to regulate neuropeptide release in\n                    <i>Caenorhabditis elegans</i>","abstract":"<jats:p>\n                    Neurons secrete neuropeptides from dense core vesicles (DCVs) to modulate neuronal activity. Little is known about how neurons manage to differentially regulate the release of synaptic vesicles (SVs) and DCVs. To analyze this, we screened all\n                    <jats:italic>Caenorhabditis elegans</jats:italic>\n                    Rab GTPases and Tre2/Bub2/Cdc16 (TBC) domain containing GTPase-activating proteins (GAPs) for defects in DCV release from\n                    <jats:italic>C. elegans</jats:italic>\n                    motoneurons.\n                    <jats:italic>rab</jats:italic>\n                    <jats:italic>-5</jats:italic>\n                    and\n                    <jats:italic>rab</jats:italic>\n                    <jats:italic>-10</jats:italic>\n                    mutants show severe defects in DCV secretion, whereas SV exocytosis is unaffected. We identified TBC-2 and TBC-4 as putative GAPs for RAB-5 and RAB-10, respectively. Multiple Rabs and RabGAPs are typically organized in cascades that confer directionality to membrane-trafficking processes. We show here that the formation of release-competent DCVs requires a reciprocal exclusion cascade coupling RAB-5 and RAB-10, in which each of the two Rabs recruits the other’s GAP molecule. This contributes to a separation of RAB-5 and RAB-10 domains at the Golgi–endosomal interface, which is lost when either of the two GAPs is inactivated. Taken together, our data suggest that RAB-5 and RAB-10 cooperate to locally exclude each other at an essential stage during DCV sorting.\n                  </jats:p>","is_dataset_classified":null,"base_score":4.143134726391533,"endowment":4.143134726391533,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23100538","pmcid":"PMC3503202","openalex_id":"https://openalex.org/W2116252656","authors":[],"funders":[{"funder_name":"NIGMS NIH HHS","grant_id":"GM067237","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R01 GM067237","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01GM067237-15","title":"Membrane Traffic in C. elegans and Mammals"},{"funder_name":"European Commission","grant_id":"201936","title":"The Synapse Nanomap"},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"39092696/GSC 226","title":"Göttingen Graduate School for Neurosciences, Biophysics and Molecular Biosciences (GGNB)"}],"total_grants":5,"fwci":1.2176,"citation_percentile":0.7491191,"influential_citations":0,"citation_trend":[{"year":2013,"count":3},{"year":2014,"count":4},{"year":2015,"count":6},{"year":2016,"count":1},{"year":2017,"count":10},{"year":2018,"count":5},{"year":2019,"count":5},{"year":2020,"count":5},{"year":2021,"count":3},{"year":2022,"count":3},{"year":2023,"count":2},{"year":2024,"count":8},{"year":2025,"count":5},{"year":2026,"count":2}],"oa_status":"bronze","license":"cc-by","oa_locations":[{"url":"https://www.pnas.org/content/pnas/109/46/18944.full.pdf","host_type":"journal"},{"url":"https://www.pnas.org/content/pnas/109/46/18944.full.pdf","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.1203306109","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.1203306109","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23100538","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3503202","host_type":"repository"},{"url":"https://resolver.sub.uni-goettingen.de/purl?gro-2/8307","host_type":"repository"},{"url":"http://dx.doi.org/10.1073/pnas.1203306109","host_type":""},{"url":"https://dx.doi.org/10.1073/pnas.1203306109","host_type":""}],"fields_of_study":["Genetics, Aging, and Longevity in Model Organisms","Cellular transport and secretion","Photoreceptor and optogenetics research","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Animals","Biological Transport","Exocytosis","Golgi Apparatus","Motor Neurons","Mutation","Neuropeptides","Endosomes","Caenorhabditis elegans","rab GTP-Binding Proteins","Secretory Vesicles","Caenorhabditis elegans Proteins","Vesicular Transport Proteins"],"keywords":["Rab","Exocytosis","GTPase","Cell biology","Caenorhabditis elegans","Biology","Secretion","Golgi apparatus","Endosome","Vesicular transport protein","Vesicle","Biochemistry","Membrane","Gene","Motor Neurons","Secretory Vesicles","Neuropeptides","Vesicular Transport Proteins","Biological Transport","Endosomes","rab GTP-Binding Proteins","Mutation","Animals","Caenorhabditis elegans Proteins"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T06:43:06.383403Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}