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Many receptors have short intracellular domains and no known link to actin. Here, we identified the \u03b21-integrin subunit and several tetraspanins (CD9, CD81, and CD151) as part of the hitherto unknown molecular link between the receptor CD36 and CA. Our data indicate that CD36 in vascular endothelial cells interacts with these proteins, with stronger interactions near the cell edge. Compromising these interactions via the point mutation G12V in the N-terminal transmembrane domain of CD36 alters the dynamic organization of CD36 on the cell surface and weakens its coupling to CA dynamics. Moreover, it abolishes thrombospondin-1\u2013induced CD36 signaling through the Src family kinase Fyn. Given their many interactions with transmembrane proteins, tetraspanins and integrins may provide a ubiquitous mechanism for plasma membrane\u2013CA coupling.<\/jats:p>","DOI":"10.1083\/jcb.202504156","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T06:21:02Z","timestamp":1782973262000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Integrins and tetraspanins mediate CD36-actin coupling and regulate CD36 organization and signaling"],"prefix":"10.1083","volume":"225","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3377-688X","authenticated-orcid":true,"given":"Soma","family":"Jana","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"UT Southwestern Medical Center 1 Department of Biophysics, , Dallas, TX,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5016-3391","authenticated-orcid":true,"given":"Huong-Tra","family":"Ngo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"UT Southwestern Medical Center 1 Department of Biophysics, , Dallas, TX,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1231-6233","authenticated-orcid":true,"given":"Han","family":"Huang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0160cpw27","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Alberta 2 Department of Biochemistry, , Edmonton,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7462-6821","authenticated-orcid":true,"given":"Jaime","family":"Guerrero","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"UT Southwestern Medical Center 1 Department of Biophysics, , Dallas, TX,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0137-4800","authenticated-orcid":true,"given":"Jesus","family":"Vega-Lugo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"UT Southwestern Medical Center 1 Department of Biophysics, , Dallas, TX,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3700-6302","authenticated-orcid":true,"given":"Nicolas","family":"Touret","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0160cpw27","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Alberta 2 Department of Biochemistry, , Edmonton,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9843-9879","authenticated-orcid":true,"given":"Aparajita","family":"Dasgupta","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"UT Southwestern Medical Center 1 Department of Biophysics, , Dallas, TX,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3471-1911","authenticated-orcid":true,"given":"Khuloud","family":"Jaqaman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"UT Southwestern Medical Center 1 Department of Biophysics, , Dallas, TX,","place":["USA"]},{"id":[{"id":"https:\/\/ror.org\/05byvp690","id-type":"ROR","asserted-by":"publisher"}],"name":"UT Southwestern Medical Center 3 Lyda Hill Department of Bioinformatics, , Dallas, TX,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"2026082109265947300_bib1","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.devcel.2013.06.019","article-title":"Advances in analysis of low signal-to-noise images link dynamin and AP2 to the functions of an endocytic checkpoint","volume":"26","author":"Aguet","year":"2013","journal-title":"Dev. 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