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

  1. Ventimiglia, Leandro N. 3
  2. Fernández-Martín, Laura 3
  3. Martínez-Alonso, Emma 1
  4. Antón, Olga M. 3
  5. Guerra, Milagros 2
  6. Martínez-Menárguez, José Angel 1
  7. Andrés, Germán 2
  8. Alonso, Miguel A. 3
  1. 1 †Departamento de Biología Celular e Histología, Facultad de Medicina, Instituto Murciano de Investigación Biosanitaria, Universidad de Murcia, 30100 Murcia, Spain; and
  2. 2 ‡Unidad de Microscopía Electrónica, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain
  3. 3 *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;
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Revista:
The Journal of Immunology

ISSN: 0022-1767,  1550-6606

Año de publicación: 2015

Volumen: 195

Número: 3

Páginas: 810-814

Tipo: Artículo

DOI: 10.4049/JIMMUNOL.1500891 GOOGLE SCHOLAR lock_openAcceso abierto editor

Otras publicaciones en: The Journal of Immunology

Resumen

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.

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