Itk controls the spatiotemporal organization of T cell activation

Kentner L Singleton, Monica Gosh, Radhika D Dandekar, Byron B Au-Yeung, Olga Ksionda, Victor L J Tybulewicz, Amnon Altman, Deborah J Fowell, Christoph Wülfing

Research output: Contribution to journalArticle (Academic Journal)

37 Citations (Scopus)

Abstract

During T cell activation by antigen-presenting cells (APCs), the diverse spatiotemporal organization of components of T cell signaling pathways modulates the efficiency of activation. Here, we found that loss of the tyrosine kinase interleukin-2 (IL-2)-inducible T cell kinase (Itk) in mice altered the spatiotemporal distributions of 14 of 16 sensors of T cell signaling molecules in the region of the interface between the T cell and the APC, which reduced the segregation of signaling intermediates into distinct spatiotemporal patterns. Activation of the Rho family guanosine triphosphatase Cdc42 at the center of the cell-cell interface was impaired, although the total cellular amount of active Cdc42 remained intact. The defect in Cdc42 localization resulted in impaired actin accumulation at the T cell-APC interface in Itk-deficient T cells. Reconstitution of cells with active Cdc42 that was specifically directed to the center of the interface restored actin accumulation in Itk-deficient T cells. Itk also controlled the central localization of the guanine nucleotide exchange factor SLAT [Switch-associated protein 70 (SWAP-70)-like adaptor of T cells], which may contribute to the activation of Cdc42 at the center of the interface. Together, these data illustrate how control of the spatiotemporal organization of T cell signaling controls critical aspects of T cell function.
Original languageEnglish
Article numberra66
JournalScience Signaling
Volume4
Issue number193
DOIs
Publication statusPublished - 4 Oct 2011

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    Singleton, K. L., Gosh, M., Dandekar, R. D., Au-Yeung, B. B., Ksionda, O., Tybulewicz, V. L. J., Altman, A., Fowell, D. J., & Wülfing, C. (2011). Itk controls the spatiotemporal organization of T cell activation. Science Signaling, 4(193), [ra66]. https://doi.org/10.1126/scisignal.2001821