RT Journal Article
T1 MAL Protein Controls Protein Sorting at the Supramolecular Activation Cluster of Human T Lymphocytes
A1 Antón Hurtado, Olga María
A1 Andrés-Delgado, Laura
A1 Reglero-Real, Natalia
A1 Batista, Alicia
A1 Alonso, Miguel
AB T cell membrane receptors and signaling molecules assemble at the immunological synapse (IS) in a supramolecular activation cluster (SMAC), organized into two differentiated subdomains: the central SMAC (cSMAC), with the TCR, Lck, and linker for activation of T cells (LAT), and the peripheral SMAC (pSMAC), with adhesion molecules. The mechanism of protein sorting to the SMAC subdomains is still unknown. MAL forms part of the machinery for protein targeting to the plasma membrane by specialized mechanisms involving condensed membranes or rafts. In this article, we report our investigation of the dynamics of MAL during the formation of the IS and its role in SMAC assembly in the Jurkat T cell line and human primary T cells. We observed that under normal conditions, a pool of MAL rapidly accumulates at the cSMAC, where it colocalized with condensed membranes, as visualized with the membrane fluorescent probe Laurdan. Mislocalization of MAL to the pSMAC greatly reduced membrane condensation at the cSMAC and redistributed machinery involved in docking microtubules or transport vesicles from the cSMAC to the pSMAC. As a consequence of these alterations, the raft-associated molecules Lck and LAT, but not the TCR, were missorted to the pSMAC. MAL, therefore, regulates membrane order and the distribution of microtubule and transport vesicle docking machinery at the IS and, by doing so, ensures correct protein sorting of Lck and LAT to the cSMAC.
PB American Association of Immunologists
SN 0022-1767
YR 2011
FD 2011
LK https://hdl.handle.net/20.500.14352/96977
UL https://hdl.handle.net/20.500.14352/96977
LA eng
NO Olga M. Antón, Laura Andrés-Delgado, Natalia Reglero-Real, Alicia Batista, Miguel A. Alonso; MAL Protein Controls Protein Sorting at the Supramolecular Activation Cluster of Human T Lymphocytes. J Immunol 1 June 2011; 186 (11): 6345–6356. https://doi.org/10.4049/jimmunol.1003771
NO Ministerio de Ciencia, Innovación y Universidades (España)
DS Docta Complutense
RD 16 abr 2025