Cutting Edge: Regulation of Exosome Secretion by the Integral MAL Protein in T Cells

• Published in: The Journal of immunology (1950) 2015-08, Vol.195 (3), p.810-814
• Main Authors: Ventimiglia, Leandro N, Fernández-Martín, Laura, Martínez-Alonso, Emma, Antón, Olga M, Guerra, Milagros, Martínez-Menárguez, José Angel, Andrés, Germán, Alonso, Miguel A
• Format: Article
• Language: English
• Subjects: Cell Line, Tumor; Cell Membrane - metabolism; HIV Infections - immunology; HIV-1 - immunology; Human immunodeficiency virus 1; Humans; Jurkat Cells; Multivesicular Bodies - immunology; Multivesicular Bodies - secretion; Myelin and Lymphocyte-Associated Proteolipid Proteins - genetics; Myelin and Lymphocyte-Associated Proteolipid Proteins - metabolism; nef Gene Products, Human Immunodeficiency Virus - immunology; T-Lymphocytes - immunology; Tetraspanin 30 - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1500891

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.