{"doi":"10.3390/cells8111388","title":"Cdc42 Couples T Cell Receptor Endocytosis to GRAF1-Mediated Tubular Invaginations of the Plasma Membrane","abstract":"<jats:p>T cell activation is immediately followed by internalization of the T cell receptor (TCR). TCR endocytosis is required for T cell activation, but the mechanisms supporting removal of TCR from the cell surface remain incompletely understood. Here we report that TCR endocytosis is linked to the clathrin-independent carrier (CLIC) and GPI-enriched endocytic compartments (GEEC) endocytic pathway. We show that unlike the canonical clathrin cargo transferrin or the adaptor protein Lat, internalized TCR accumulates in tubules shaped by the small GTPase Cdc42 and the Bin/amphiphysin/Rvs (BAR) domain containing protein GRAF1 in T cells. Preventing GRAF1-positive tubules to mature into endocytic vesicles by expressing a constitutively active Cdc42 impairs the endocytosis of TCR, while having no consequence on the uptake of transferrin. Together, our data reveal a link between TCR internalization and the CLIC/GEEC endocytic route supported by Cdc42 and GRAF1.</jats:p>","journal":"Cells","year":2019,"id":30442,"datarank":0.7120252948898005,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.26266545385670187,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.26266545385670187,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":14,"citers_with_citation_signal":11,"citers_with_endowment":11,"datacite_reuse_total":6,"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":165324,"name":"Luca Ziegler","orcid":null,"position":1,"is_corresponding":false},{"id":165325,"name":"Richard Schregle","orcid":null,"position":2,"is_corresponding":false},{"id":165326,"name":"Verena M. Betzler","orcid":null,"position":3,"is_corresponding":false},{"id":165327,"name":"Manuela Ecker","orcid":null,"position":4,"is_corresponding":false},{"id":165328,"name":"Jérémie Rossy","orcid":"0000-0002-5128-5283","position":5,"is_corresponding":false},{"id":165323,"name":"Pascal Rossatti","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.995732273553991,"endowment":2.995732273553991,"datacite_reuse_total":6,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31690048","pmcid":"PMC6912536","openalex_id":"https://openalex.org/W2987529999","authors":[],"funders":[{"funder_name":"Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung","grant_id":"SNSF172969","title":null},{"funder_name":"National Health and Medical Research Council","grant_id":"APP1102730","title":null},{"funder_name":"Thurgauische Stiftung für Wissenschaft und Forschung","grant_id":"NA","title":null},{"funder_name":"Swiss National Science Foundation","grant_id":"172969","title":"Understanding the role of endosomes in T cells"},{"funder_name":"National Health and Medical Research Council (NHMRC)","grant_id":"1102730","title":"A signalling endosomal network in T cell activation"}],"total_grants":5,"fwci":1.6989,"citation_percentile":0.82384734,"influential_citations":1,"citation_trend":[{"year":2020,"count":2},{"year":2021,"count":6},{"year":2022,"count":7},{"year":2025,"count":4}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2073-4409/8/11/1388/pdf?version=1574315227","host_type":"journal"},{"url":"https://www.mdpi.com/2073-4409/8/11/1388/pdf?version=1574315227","host_type":"GOLD"},{"url":"https://www.mdpi.com/2073-4409/8/11/1388/pdf?version=1574315227","host_type":"publisher"},{"url":"https://www.mdpi.com/2073-4409/8/11/1388/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/cells8111388","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31690048","host_type":"repository"},{"url":"https://doaj.org/article/fba9da09679d4992b3eab52372ef8510","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6912536","host_type":"repository"},{"url":"http://nbn-resolving.de/urn:nbn:de:bsz:352-2-uftfiuu2i1ij7","host_type":"repository"},{"url":"http://dx.doi.org/10.3390/cells8111388","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC6912536","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC6912536?pdf=render","host_type":"Europe_PMC"},{"url":"https://dx.doi.org/10.3390/cells8111388","host_type":""},{"url":"https://sonar.ch/global/documents/248755","host_type":""}],"fields_of_study":["Cellular transport and secretion","Glycosylation and Glycoproteins Research","Monoclonal and Polyclonal Antibodies Research","Chemistry","Medicine","Biology","0301 basic medicine","03 medical and health sciences","0303 health sciences","Cell Line, Tumor","Cell Membrane","Clathrin","Endocytosis","GTPase-Activating Proteins","Humans","Jurkat Cells","Receptors, Antigen, T-Cell","T-Lymphocytes","cdc42 GTP-Binding Protein"],"mesh_terms":["Cell Membrane","Clathrin","Endocytosis","Humans","Receptors, Antigen, T-Cell","T-Lymphocytes","Jurkat Cells","GTPase-Activating Proteins","cdc42 GTP-Binding Protein","Cell Line, Tumor"],"keywords":["Endocytic cycle","Endocytosis","Internalization","Cell biology","T-cell receptor","Amphiphysin","Receptor-mediated endocytosis","CDC42","Transferrin receptor","Clathrin","Biology","Dynamin","Endosome","Transferrin","T cell","Chemistry","GTPase","Receptor","Biochemistry","Intracellular","Immunology","Immune system","T cell receptor","Clic","Clathrin-independent Endocytosis","Graf1","T cell receptor; clathrin-independent endocytosis; CLIC; Cdc42; GRAF1","T-Lymphocytes","Receptors, Antigen, T-Cell","Article","Jurkat Cells","Cell Line, Tumor","Humans","cdc42 GTP-Binding Protein","info:eu-repo/classification/ddc/570","QH573-671","Cell Membrane","GTPase-Activating Proteins","Cytology"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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