title: Cutting Edge: Regulation of Exosome Secretion by the Integral MAL Protein in T Cells.
abstract: 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.
authors.affiliation: Departamento de Biología Celular e Inmunología, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain;
authors.forename: Leandro N
authors.initials: LN
authors.lastname: Ventimiglia
authors.affiliation: Departamento de Biología Celular e Inmunología, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain;
authors.forename: Laura
authors.initials: L
authors.lastname: Fernández-Martín
authors.affiliation: Departamento de Biología Celular e Histología, Facultad de Medicina, Instituto Murciano de Investigación Biosanitaria, Universidad de Murcia, 30100 Murcia, Spain; and.
authors.forename: Emma
authors.initials: E
authors.lastname: Martínez-Alonso
authors.affiliation: Departamento de Biología Celular e Inmunología, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain;
authors.forename: Olga M
authors.initials: OM
authors.lastname: Antón
authors.affiliation: Unidad de Microscopía Electrónica, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Milagros
authors.initials: M
authors.lastname: Guerra
authors.affiliation: Departamento de Biología Celular e Histología, Facultad de Medicina, Instituto Murciano de Investigación Biosanitaria, Universidad de Murcia, 30100 Murcia, Spain; and.
authors.forename: José Angel
authors.initials: JA
authors.lastname: Martínez-Menárguez
authors.affiliation: Unidad de Microscopía Electrónica, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Germán
authors.initials: G
authors.lastname: Andrés
authors.affiliation: Departamento de Biología Celular e Inmunología, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain; maalonso@cbm.csic.es.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Alonso
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D057146:Multivesicular Bodies / Q000276:immunology / Q000378:metabolism*; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D060149:Tetraspanin 30 / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: C554586:CD63 protein, human; C569026:MAL protein, human; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D060149:Tetraspanin 30; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1