{"doi":"10.1111/tra.12302","title":"Sorting of Clathrin‐Independent Cargo Proteins Depends on Rab35 Delivered by Clathrin‐Mediated Endocytosis","abstract":"<jats:title>Abstract</jats:title><jats:p>Clathrin‐mediated endocytosis (<jats:styled-content style=\"fixed-case\">CME</jats:styled-content>) and clathrin‐independent endocytosis (<jats:styled-content style=\"fixed-case\">CIE</jats:styled-content>) co‐exist in most cells but little is known about their communication and coordination. Here we show that when <jats:styled-content style=\"fixed-case\">CME</jats:styled-content> was inhibited, endocytosis by <jats:styled-content style=\"fixed-case\">CIE</jats:styled-content> continued but endosomal trafficking of <jats:styled-content style=\"fixed-case\">CIE</jats:styled-content> cargo proteins was altered. <jats:styled-content style=\"fixed-case\">CIE</jats:styled-content> cargo proteins that normally traffic directly into Arf6‐associated tubules after internalization and avoid degradation (<jats:styled-content style=\"fixed-case\">CD44</jats:styled-content>, <jats:styled-content style=\"fixed-case\">CD98</jats:styled-content> and <jats:styled-content style=\"fixed-case\">CD147</jats:styled-content>) now trafficked to lysosomes and were degraded. The endosomal tubules were also absent and Arf6‐<jats:styled-content style=\"fixed-case\">GTP</jats:styled-content> levels were elevated. The altered trafficking, loss of the tubular endosomal network and elevated Arf6‐<jats:styled-content style=\"fixed-case\">GTP</jats:styled-content> levels caused by inhibition of <jats:styled-content style=\"fixed-case\">CME</jats:styled-content> were rescued by expression of Rab35, a Rab associated with clathrin‐coated vesicles, or its effector <jats:styled-content style=\"fixed-case\">ACAPs</jats:styled-content>, Arf6 <jats:styled-content style=\"fixed-case\">GTPase</jats:styled-content> activating proteins (<jats:styled-content style=\"fixed-case\">GAP</jats:styled-content>) that inactivate Arf6. Furthermore, <jats:styled-content style=\"fixed-case\">siRNA</jats:styled-content> knockdown of Rab35 recreated the phenotype of <jats:styled-content style=\"fixed-case\">CME</jats:styled-content> ablation on <jats:styled-content style=\"fixed-case\">CIE</jats:styled-content> cargo trafficking without altering endocytosis of transferrin. These observations suggest that Rab35 serves as a <jats:styled-content style=\"fixed-case\">CME</jats:styled-content> detector and that loss of <jats:styled-content style=\"fixed-case\">CME</jats:styled-content>, or Rab35 input, leads to elevated Arf6‐<jats:styled-content style=\"fixed-case\">GTP</jats:styled-content> and shifts the sorting of <jats:styled-content style=\"fixed-case\">CIE</jats:styled-content> cargo proteins to lysosomes and degradation.</jats:p><jats:p><jats:inline-graphic xmlns:xlink=\"http://www.w3.org/1999/xlink\" xlink:href=\"graphic/tra12302-gra-0001.png\" xlink:title=\"image\"/></jats:p>","journal":"Traffic","year":2015,"id":24631,"datarank":2.402616786601209,"base_score":4.07753744390572,"endowment":4.07753744390572,"self_citation_contribution":0.611630616585858,"citation_network_contribution":1.7909861700153513,"self_endowment_contribution":0.611630616585858,"citer_contribution":1.7909861700153513,"corpus_percentile":null,"corpus_rank":null,"citation_count":58,"citer_count":53,"citers_with_citation_signal":48,"citers_with_endowment":48,"datacite_reuse_total":14,"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":147253,"name":"Julie G. Donaldson","orcid":null,"position":1,"is_corresponding":false},{"id":147252,"name":"Dipannita Dutta","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.07753744390572,"endowment":4.07753744390572,"datacite_reuse_total":14,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25988331","pmcid":"PMC4543536","openalex_id":"https://openalex.org/W1694039885","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"HL006130","title":null},{"funder_name":"Intramural NIH HHS","grant_id":"ZIA HL006130","title":null}],"total_grants":2,"fwci":3.4535,"citation_percentile":0.92288774,"influential_citations":5,"citation_trend":[{"year":2015,"count":2},{"year":2016,"count":6},{"year":2017,"count":5},{"year":2018,"count":9},{"year":2019,"count":9},{"year":2020,"count":4},{"year":2021,"count":5},{"year":2022,"count":4},{"year":2023,"count":2},{"year":2024,"count":6},{"year":2025,"count":6}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/tra.12302","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/tra.12302","host_type":"BRONZE"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/tra.12302","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Ftra.12302","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/tra.12302","host_type":"publisher"},{"url":"https://doi.org/10.1111/tra.12302","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25988331","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4543536","host_type":"repository"}],"fields_of_study":["Cellular transport and secretion","Lipid Membrane Structure and Behavior","Erythrocyte Function and Pathophysiology","Medicine","Biology","ADP-Ribosylation Factor 6","ADP-Ribosylation Factors","Clathrin-Coated Vesicles","Endocytosis","Endosomes","GTPase-Activating Proteins","HeLa Cells","Humans","Lysosomes","Protein Transport","Transferrin","rab GTP-Binding Proteins"],"mesh_terms":["ADP-Ribosylation Factor 6","Endocytosis","HeLa Cells","Humans","Lysosomes","Endosomes","Transferrin","GTPase-Activating Proteins","rab GTP-Binding Proteins","ADP-Ribosylation Factors","Protein Transport","Clathrin-Coated Vesicles","Hela Cells"],"keywords":["Endocytosis","Clathrin","Rab","Endosome","Cell biology","Biology","ADP ribosylation factor","Signal transducing adaptor protein","Internalization","Clathrin adaptor proteins","Exocytosis","Small GTPase","GTPase","Intracellular","Signal transduction","Biochemistry","Golgi apparatus","Receptor","Secretion","Lysosomes","CD147","Cargo Sorting","Arf6","Rab35","Clathrin-mediated Endocytosis","Clathrin-independent Endocytosis","Cd98"],"sdg_mappings":[],"linked_datasets":[{"doi":"10.6084/m9.figshare.25522647.v1","title":"Additional file 1 of Physiological and transcriptomic comparisons shed light on the cold stress response mechanisms of Dendrobium spp","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.25522647","title":"Additional file 1 of Physiological and transcriptomic comparisons shed light on the cold stress response mechanisms of Dendrobium spp","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26700403","title":"Additional file 7 of Physiological and transcriptomic comparisons shed light on the cold stress response mechanisms of Dendrobium spp","publisher":"figshare","resource_type":"Dataset"},{"doi":"10.6084/m9.figshare.26700403.v1","title":"Additional file 7 of Physiological and transcriptomic comparisons shed light on the cold stress 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