{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T22:04:44Z","timestamp":1789941884449,"version":"4.0.1"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Exosomes secreted by T cells play an important role in coordinating the immune response. HIV-1 Nef hijacks the route of exosome secretion of T cells to modulate the functioning of uninfected cells. Despite the importance of the process, the protein machinery involved in exosome biogenesis is yet to be identified. In this study, we show that MAL, a tetraspanning membrane protein expressed in human T cells, is present in endosomes that travel toward the plasma membrane for exosome secretion. In the absence of MAL, the release of exosome particles and markers was greatly impaired. This effect was accompanied by protein sorting defects at multivesicular endosomes that divert the exosomal marker CD63 to autophagic vacuoles. Exosome release induced by HIV-1 Nef was also dependent on MAL expression. Therefore, MAL is a critical element of the machinery for exosome secretion and may constitute a target for modulating exosome secretion by human T cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1500891","type":"journal-article","created":{"date-parts":[[2015,6,25]],"date-time":"2015-06-25T01:36:11Z","timestamp":1435196171000},"page":"810-814","source":"Crossref","is-referenced-by-count":39,"title":["Cutting Edge: Regulation of Exosome Secretion by the Integral MAL Protein in T Cells"],"prefix":"10.1093","volume":"195","author":[{"given":"Leandro N","family":"Ventimiglia","sequence":"first","affiliation":[{"name":"Departamento de Biolog\u00eda Celular e Inmunolog\u00eda, Centro de Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas, Universidad Aut\u00f3noma de Madrid , Cantoblanco, 28049 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Fern\u00e1ndez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular e Inmunolog\u00eda, Centro de Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas, Universidad Aut\u00f3noma de Madrid , Cantoblanco, 28049 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Mart\u00ednez-Alonso","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular e Histolog\u00eda, Facultad de Medicina, Instituto Murciano de Investigaci\u00f3n Biosanitaria, Universidad de Murcia , 30100 Murcia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga M","family":"Ant\u00f3n","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular e Inmunolog\u00eda, Centro de Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas, Universidad Aut\u00f3noma de Madrid , Cantoblanco, 28049 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milagros","family":"Guerra","sequence":"additional","affiliation":[{"name":"Unidad de Microscop\u00eda Electr\u00f3nica, Centro de Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas, Universidad Aut\u00f3noma de Madrid , Cantoblanco, 28049 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Angel","family":"Mart\u00ednez-Men\u00e1rguez","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular e Histolog\u00eda, Facultad de Medicina, Instituto Murciano de Investigaci\u00f3n Biosanitaria, Universidad de Murcia , 30100 Murcia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germ\u00e1n","family":"Andr\u00e9s","sequence":"additional","affiliation":[{"name":"Unidad de Microscop\u00eda Electr\u00f3nica, Centro de Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas, Universidad Aut\u00f3noma de Madrid , Cantoblanco, 28049 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A","family":"Alonso","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Celular e Inmunolog\u00eda, Centro de Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas, Universidad Aut\u00f3noma de Madrid , Cantoblanco, 28049 Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,8,1]]},"reference":[{"key":"2025030703555263100_r1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1083\/jcb.201211138","article-title":"Extracellular vesicles: exosomes, microvesicles, and friends","volume":"200","author":"Raposo","year":"2013","journal-title":"J. Cell Biol."},{"key":"2025030703555263100_r2","doi-asserted-by":"crossref","first-page":"11529","DOI":"10.1128\/JVI.01712-14","article-title":"Exosomes from human immunodeficiency virus type 1 (HIV-1)-infected cells license quiescent CD4+ T lymphocytes to replicate HIV-1 through a Nef- and ADAM17-dependent mechanism","volume":"88","author":"Arenaccio","year":"2014","journal-title":"J. Virol."},{"key":"2025030703555263100_r3","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/1742-4690-11-46","article-title":"Cell activation and HIV-1 replication in unstimulated CD4+ T lymphocytes ingesting exosomes from cells expressing defective HIV-1","volume":"11","author":"Arenaccio","year":"2014","journal-title":"Retrovirology"},{"key":"2025030703555263100_r4","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.immuni.2014.05.019","article-title":"MicroRNA-containing T-regulatory-cell-derived exosomes suppress pathogenic T helper 1 cells","volume":"41","author":"Okoye","year":"2014","journal-title":"Immunity"},{"key":"2025030703555263100_r5","doi-asserted-by":"crossref","first-page":"555","DOI":"10.3389\/fimmu.2014.00555","article-title":"Regulatory T cell-derived exosomes: possible therapeutic and diagnostic tools in transplantation","volume":"5","author":"Agarwal","year":"2014","journal-title":"Front. Immunol."},{"key":"2025030703555263100_r6","doi-asserted-by":"crossref","first-page":"518","DOI":"10.3389\/fimmu.2014.00518","article-title":"Immunotherapeutic potential of extracellular vesicles","volume":"5","author":"Zhang","year":"2014","journal-title":"Front. Immunol."},{"key":"2025030703555263100_r7","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1146\/annurev-cellbio-092910-154152","article-title":"Multivesicular body morphogenesis","volume":"28","author":"Hanson","year":"2012","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2025030703555263100_r8","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/nature08849","article-title":"Molecular mechanism of multivesicular body biogenesis by ESCRT complexes","volume":"464","author":"Wollert","year":"2010","journal-title":"Nature"},{"key":"2025030703555263100_r9","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/ncb2502","article-title":"Syndecan-syntenin-ALIX regulates the biogenesis of exosomes","volume":"14","author":"Baietti","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"2025030703555263100_r10","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1126\/science.1153124","article-title":"Ceramide triggers budding of exosome vesicles into multivesicular endosomes","volume":"319","author":"Trajkovic","year":"2008","journal-title":"Science"},{"key":"2025030703555263100_r11","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1038\/ncomms1285","article-title":"Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells","volume":"2","author":"Mittelbrunn","year":"2011","journal-title":"Nat. Commun."},{"key":"2025030703555263100_r12","doi-asserted-by":"crossref","first-page":"3201","DOI":"10.1084\/jem.20080552","article-title":"An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes","volume":"205","author":"Ant\u00f3n","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025030703555263100_r13","doi-asserted-by":"crossref","first-page":"6345","DOI":"10.4049\/jimmunol.1003771","article-title":"MAL protein controls protein sorting at the supramolecular activation cluster of human T lymphocytes","volume":"186","author":"Ant\u00f3n","year":"2011","journal-title":"J. Immunol."},{"key":"2025030703555263100_r14","doi-asserted-by":"crossref","first-page":"3675","DOI":"10.1002\/(SICI)1521-4141(199811)28:11<3675::AID-IMMU3675>3.0.CO;2-5","article-title":"MAL, a novel integral membrane protein of human T lymphocytes, associates with glycosylphosphatidylinositol-anchored proteins and Src-like tyrosine kinases","volume":"28","author":"Mill\u00e1n","year":"1998","journal-title":"Eur. J. Immunol."},{"key":"2025030703555263100_r15","doi-asserted-by":"crossref","DOI":"10.1002\/0471143030.cb0322s30","volume-title":"Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological Fluids.","author":"Th\u00e9ry","year":"2006"},{"key":"2025030703555263100_r16","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.chom.2009.06.009","article-title":"Massive secretion by T cells is caused by HIV Nef in infected cells and by Nef transfer to bystander cells","volume":"6","author":"Muratori","year":"2009","journal-title":"Cell Host Microbe"},{"key":"2025030703555263100_r17","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1111\/j.1600-0854.2009.01006.x","article-title":"HIV Nef is secreted in exosomes and triggers apoptosis in bystander CD4+ T cells","volume":"11","author":"Lenassi","year":"2010","journal-title":"Traffic"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/195\/3\/810\/62252110\/1500891.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/195\/3\/810\/62252110\/1500891.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T03:56:05Z","timestamp":1741319765000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/195\/3\/810\/7973318"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,8,1]]},"references-count":17,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,8,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1500891","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2015,8]]},"published":{"date-parts":[[2015,8,1]]}}}