Itk Functions to Control Actin Polymerization at the Immune Synapse Through Localized Activation of Cdc42 and WASP

Overview

Journal Curr Biol

Publisher Cell Press

Specialty Biology

Date 2003 Sep 19

PMID 13678593

Citations 53

Authors

Christine M Labno

Carol M Lewis

Daoqi You

Daisy W Leung

Ana Takesono

Natalie Kamberos

Abhinav Seth

Lisa D Finkelstein

Michael K Rosen

Pamela L Schwartzberg

Janis K Burkhardt

Affiliations

Soon will be listed here.

Abstract

Actin polymerization at the immune synapse is required for T cell activation and effector function; however, the relevant regulatory pathways remain poorly understood. We showed previously that binding to antigen presenting cells (APCs) induces localized activation of Cdc42 and Wiskott-Aldrich Syndrome protein (WASP) at the immune synapse. Several lines of evidence suggest that Tec kinases could interact with WASP-dependent actin regulatory processes. Since T cells from Rlk-/-, Itk-/-, and Rlk-/- x Itk-/- mice have defects in signaling and development, we asked whether Itk or Rlk function in actin polymerization at the immune synapse. We find that Itk-/- and Rlk-/- x Itk-/- T cells are defective in actin polymerization and conjugate formation in response to antigen-pulsed APCs. Itk functions downstream of the TCR, since similar defects were observed upon TCR engagement alone. Using conformation-specific probes, we show that although the recruitment of WASP and Arp2/3 complex to the immune synapse proceeds normally, the localized activation of Cdc42 and WASP is defective. Finally, we find that the defect in Cdc42 activation likely stems from a requirement for Itk in the recruitment of Vav to the immune synapse. Our results identify Itk as a key element of the pathway leading to localized actin polymerization at the immune synapse.

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