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oai:docta.ucm.es:20.500.14352/969772024-08-09T23:58:46Zcom_20.500.14352_14col_20.500.14352_15

00925njm 22002777a 4500 dc Antón Hurtado, Olga María author Andrés-Delgado, Laura author Reglero-Real, Natalia author Batista, Alicia author Alonso, Miguel author 2011 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. 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 0022-1767 10.4049/jimmunol.1003771 https://hdl.handle.net/20.500.14352/96977 1550-6606 https://doi.org/10.4049/jimmunol.1003771 MAL Protein Controls Protein Sorting at the Supramolecular Activation Cluster of Human T Lymphocytes