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Ezrin tunes T‐cell activation by controlling Dlg1 and microtubule positioning at the immunological synapse
Author(s) -
Lasserre Rémi,
Charrin Stéphanie,
Cuche Céline,
Danckaert Anne,
Thoulouze MariaIsabel,
de Chaumont Fabrice,
Duong Tarn,
Perrault Nathalie,
VarinBlank Nadine,
OlivoMarin JeanChristophe,
EtienneManneville Sandrine,
Arpin Monique,
Di Bartolo Vincenzo,
Alcover Andrés
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.127
Subject(s) - biology , ezrin , microtubule , immunological synapse , microbiology and biotechnology , synapse , cell , genetics , cytoskeleton , neuroscience , immune system , t cell , t cell receptor
T‐cell receptor (TCR) signalling is triggered and tuned at immunological synapses by the generation of signalling complexes that associate into dynamic microclusters. Microcluster movement is necessary to tune TCR signalling, but the molecular mechanism involved remains poorly known. We show here that the membrane‐microfilament linker ezrin has an important function in microcluster dynamics and in TCR signalling through its ability to set the microtubule network organization at the immunological synapse. Importantly, ezrin and microtubules are important to down‐regulate signalling events leading to Erk1/2 activation. In addition, ezrin is required for appropriate NF‐AT activation through p38 MAP kinase. Our data strongly support the notion that ezrin regulates immune synapse architecture and T‐cell activation through its interaction with the scaffold protein Dlg1. These results uncover a crucial function for ezrin, Dlg1 and microtubules in the organization of the immune synapse and TCR signal down‐regulation. Moreover, they underscore the importance of ezrin and Dlg1 in the regulation of NF‐AT activation through p38.