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

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

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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 [1]. Several lines of evidence suggest that Tec kinases could interact with WASP-dependent actin regulatory processes [2]. Since T cells from RIk-/-, Itk-/-, and RIk-/- x Itk-/- mice have defects in signaling and development [3], we asked whether Itk or RIk function in actin polymerization at the immune synapse. We find that Itk-/- and RIk-/- 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.

Original languageEnglish (US)
Pages (from-to)1619-1624
Number of pages6
JournalCurrent Biology
Volume13
Issue number18
DOIs
StatePublished - Sep 16 2003

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Labno, C. M., Lewis, C. M., You, D., Leung, D. W., Takesono, A., Kamberos, N., Seth, A., Finkelstein, L. D., Rosen, M. K., Schwartzberg, P. L., & Burkhardt, J. K. (2003). Itk functions to control actin polymerization at the immune synapse through localized activation of Cdc42 and WASP. Current Biology, 13(18), 1619-1624. https://doi.org/10.1016/j.cub.2003.08.005