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Furthermore, we show that syntenin, a previously described exosome biogenesis factor, drives the vesicular secretion of CD63 by blocking CD63 endocytosis and that other endocytosis inhibitors also induce the plasma membrane accumulation and vesicular secretion of CD63. Finally, we show that CD63 is an expression-dependent inhibitor of endocytosis that triggers the vesicular secretion of lysosomal proteins and the clathrin adaptor AP-2 mu2. These results suggest that the vesicular secretion of exosome marker proteins in exosome-sized vesicles occurs primarily by an endocytosis-independent pathway.<\/jats:p>","DOI":"10.1126\/sciadv.adi9156","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T13:59:36Z","timestamp":1715176776000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":75,"title":["Endocytosis blocks the vesicular secretion of exosome marker proteins"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3359-5464","authenticated-orcid":true,"given":"Yiwei","family":"Ai","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, 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