Itk functions to control actin polymerization at the immune synapse through localized activation of Cdc42 and WASP Journal Article
| Authors: | 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. |
| Article Title: | 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 [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. |
| Keywords: | oncoprotein; proto-oncogene proteins; t lymphocyte; t-lymphocytes; proteins; cell cycle protein; mouse; animal; cytology; metabolism; animals; cell cycle proteins; mice; actin; spleen; protein; enzyme activation; protein tyrosine kinase; physiology; animalia; immunology; fluorescence microscopy; microscopy, fluorescence; protein-tyrosine kinases; immunity; actins; antigen presenting cell; antigen-presenting cells; protein cdc42; wiskott aldrich syndrome protein; vav protein; cdc42 gtp-binding protein; proto-oncogene proteins c-vav; wiskott-aldrich syndrome protein; article; emt protein tyrosine kinase; emt protein-tyrosine kinase; vav1 protein, mouse; was protein, mouse; vespidae |
| Journal Title: | Current Biology |
| Volume: | 13 |
| Issue: | 18 |
| ISSN: | 0960-9822 |
| Publisher: | Cell Press |
| Date Published: | 2003-09-16 |
| Start Page: | 1619 |
| End Page: | 1624 |
| Language: | English |
| DOI: | 10.1016/j.cub.2003.08.005 |
| PUBMED: | 13678593 |
| PROVIDER: | scopus |
| PMCID: | PMC3417328 |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
