{"doi":"10.1242/jcs.156299","title":"Identification of molecular heterogeneity in SNX27-retromer-mediated endosome-to-plasma membrane recycling","abstract":"<jats:p>Retromer is a protein assembly that orchestrates sorting of transmembrane cargo proteins into endosome-to-Golgi and endosome-to-plasma membrane transport pathways. Here, we have employed quantitative proteomics to define the interactome of human VPS35, the core retromer component. This has identified a number of new interacting proteins, including ankyrin-repeat domain 50 (ANKRD50), seriologically-defined colon cancer antigen 3 (SDCCAG3) and VPS9-ankyrin-repeat protein (VARP). Depletion of these proteins resulted in trafficking defects of retromer-dependent cargo, but differential and cargo specific effects suggested a surprising degree of functional heterogeneity in retromer-mediated endosome-to-plasma membrane sorting. Extending this, suppression of the retromer-associated WASH complex did not uniformly affect retromer cargo, thereby confirming cargo specific functions for retromer interacting proteins. Further analysis of the retromer-VARP interaction identified a role for retromer in endosome-to-melanosome transport. Suppression of VPS35 led to miss trafficking of the melanogenic enzymes, tyrosinase and tryrosine-related protein 1 (Tyrp1), establishing that retromer acts in concert with VARP in this trafficking pathway. Overall these data reveal hidden complexities in retromer-mediated sorting and open up new directions in our molecular understanding of this essential sorting complex.</jats:p>","journal":"Journal of Cell Science","year":2014,"id":600198,"datarank":0.7050720548688626,"base_score":4.700480365792417,"endowment":4.700480365792417,"self_citation_contribution":0.7050720548688626,"citation_network_contribution":0.0,"self_endowment_contribution":0.7050720548688626,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":109,"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":1538579,"name":"Florian Steinberg","orcid":null,"position":1,"is_corresponding":false},{"id":146711,"name":"Matthew Gallon","orcid":null,"position":2,"is_corresponding":false},{"id":1538580,"name":"Ayaka Yatsu","orcid":null,"position":3,"is_corresponding":false},{"id":427417,"name":"Norihiko Ohbayashi","orcid":null,"position":4,"is_corresponding":false},{"id":483205,"name":"Kate J. 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This has identified a number of new interacting proteins, including ankyrin-repeat domain 50 (ANKRD50), seriologically-defined colon cancer antigen 3 (SDCCAG3) and VPS9-ankyrin-repeat protein (VARP). Depletion of these proteins resulted in trafficking defects of retromer-dependent cargo, but differential and cargo specific effects suggested a surprising degree of functional heterogeneity in retromer-mediated endosome-to-plasma membrane sorting. Extending this, suppression of the retromer-associated WASH complex did not uniformly affect retromer cargo, thereby confirming cargo specific functions for retromer interacting proteins. Further analysis of the retromer-VARP interaction identified a role for retromer in endosome-to-melanosome transport. Suppression of VPS35 led to miss trafficking of the melanogenic enzymes, tyrosinase and tryrosine-related protein 1 (Tyrp1), establishing that retromer acts in concert with VARP in this trafficking pathway. Overall these data reveal hidden complexities in retromer-mediated sorting and open up new directions in our molecular understanding of this essential sorting complex.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25278552","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"Wellcome Trust","grant_id":"089928","title":"Towards a thorough mechanistic understanding of phosphoinositide-mediated endosomal sorting."}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"hybrid","license":"cc-by","oa_locations":[{"url":"https://jcs.biologists.org/content/joces/127/22/4940.full.pdf","host_type":"publisher"},{"url":"http://journals.biologists.com/jcs/article-pdf/127/22/4940/1936876/jcs-127-22-4940.pdf","host_type":"publisher"},{"url":"http://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.156299/2046839/jcs156299.pdf","host_type":"publisher"},{"url":"https://research-information.bris.ac.uk/en/publications/57c9ca4e-d2ad-4e37-b88c-bea65f32c211","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4231307","host_type":"repository"},{"url":"https://doi.org/10.1242/jcs.156299","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/25278552","host_type":""},{"url":"http://dx.doi.org/10.1242/jcs.156299","host_type":""},{"url":"https://dx.doi.org/10.1242/jcs.156299","host_type":""},{"url":"https://hdl.handle.net/1983/57c9ca4e-d2ad-4e37-b88c-bea65f32c211","host_type":""},{"url":"https://research-information.bris.ac.uk/ws/files/221090397/4940.full.pdf","host_type":""},{"url":"https://doi.org/https://doi.org/10.1242/jcs.156299","host_type":""}],"fields_of_study":["0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":[],"keywords":["Cell Membrane","Transferrin","Vesicular Transport Proteins","610","Endosomes","Transfection","Protein Transport","rab GTP-Binding Proteins","Humans","Sorting Nexins","Research Article","HeLa Cells"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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