Ezrin tunes T-cell activation by controlling Dlg1 and microtubule positioning at the immunological synapse.

Rémi Lasserre; Stephanie Charrin; Céline Cuche; Anne Danckaert; Maria-Isabel Thoulouze; Fabrice de Chaumont; Tarn Duong; Nathalie Perrault; Nadine Varin-Blank; Jean-Christophe Olivo-Marin; Sandrine Etienne-Manneville; Monique Arpin; Vincenzo Di Bartolo; Andrès Alcover

doi:10.1038/emboj.2010.127

Journal articles

Ezrin tunes T-cell activation by controlling Dlg1 and microtubule positioning at the immunological synapse.

Rémi Lasserre ¹ Stephanie Charrin ¹ Céline Cuche ¹ Anne Danckaert ² Maria-Isabel Thoulouze ¹ Fabrice de Chaumont ³ Tarn Duong ⁴ Nathalie Perrault ⁵ Nadine Varin-Blank ⁵ Jean-Christophe Olivo-Marin ³ Sandrine Etienne-Manneville ⁶ Monique Arpin ⁷ Vincenzo Di Bartolo ¹ Andrès Alcover ^{1, *}

* Corresponding author

1 BIOCELLY - Biologie Cellulaire des Lymphocytes

2 PFID - Imagerie Dynamique (Plate-Forme)

3 AIQ - Analyse d'Images Quantitative

4 Imagerie et Modélisation

5 UMR_S567 / UMR 8104 - Institut Cochin

6 Polarité et Migration Cellulaires

7 Morphogénèse et Signalisation Cellulaires

Abstract : 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.

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Journal articles

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Life Sciences [q-bio] / Microbiology and Parasitology

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Ezrin tunes T-cell activation by controlling Dlg1 and microtubule positioning at the immunological synapse.

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Ezrin tunes T-cell activation by controlling Dlg1 and microtubule positioning at the immunological synapse.

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