HS1 Functions As an Essential Actin-regulatory Adaptor Protein at the Immune Synapse

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2006 Jun 20

PMID 16782030

Citations 112

Authors

Timothy S Gomez

Sean D McCarney

Esteban Carrizosa

Christine M Labno

Erin O Comiskey

Jeffrey C Nolz

Peimin Zhu

Bruce D Freedman

Marcus R Clark

David J Rawlings

Daniel D Billadeau

Janis K Burkhardt

Affiliations

Soon will be listed here.

Abstract

HS1, the leukocyte-specific homolog of cortactin, regulates F-actin in vitro and is phosphorylated in response to TCR ligation, but its role in lymphocyte activation has not been addressed. We demonstrate that HS1-deficient T cells fail to accumulate F-actin at the immune synapse (IS) and, upon TCR ligation, form actin-rich structures that are disordered and unstable. Early TCR activation events are intact in these cells, but Ca2+ influx and IL-2 gene transcription are defective. Importantly, HS1 tyrosine phosphorylation is required for its targeting to the IS and for its function in regulating actin dynamics and IL-2 promoter activity. Phosphorylation also links HS1 to multiple signaling proteins, including Lck, PLCgamma1, and Vav1, and is essential for the stable recruitment of Vav1 to the IS. Taken together, our studies show that HS1 is indispensable for signaling events leading to actin assembly and IL-2 production during T cell activation.

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