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Itk functions to control actin polymerization at the immune synapse through localized activation of Cdc42 and WASP.


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.

SUBMITTER: Labno CM 

PROVIDER: S-EPMC3417328 | biostudies-literature | 2003 Sep

REPOSITORIES: biostudies-literature

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Itk functions to control actin polymerization at the immune synapse through localized activation of Cdc42 and WASP.

Labno Christine M CM   Lewis Carol M CM   You Daoqi D   Leung Daisy W DW   Takesono Ana A   Kamberos Natalie N   Seth Abhinav A   Finkelstein Lisa D LD   Rosen Michael K MK   Schwartzberg Pamela L PL   Burkhardt Janis K JK  

Current biology : CB 20030901 18


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-/  ...[more]

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