Research ArticleTCR Signaling

RIAM Regulates the Cytoskeletal Distribution and Activation of PLC-γ1 in T Cells

Sci. Signal.  01 Dec 2009:
Vol. 2, Issue 99, pp. ra79
DOI: 10.1126/scisignal.2000409

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Abstract

Rap1–guanosine triphosphate (GTP)–interacting adaptor molecule (RIAM) plays a critical role in actin reorganization and inside-out activation of integrins in lymphocytes and platelets. We investigated the role of RIAM in T cell receptor (TCR)–mediated signaling. Although phosphorylation of the kinase ZAP-70 and formation of a signalosome recruited to the adaptor protein LAT were unaffected, elimination of endogenous RIAM by short hairpin RNA impaired generation of inositol 1,4,5-trisphosphate, mobilization of intracellular calcium ions (Ca2+), and translocation of the transcription factor NFAT to the nucleus. The activation of Ras guanine nucleotide–releasing protein 1 was also impaired, which led to the diminished expression of the gene encoding interleukin-2. These events were associated with the impaired translocation of phosphorylated phospholipase C–γ1 (PLC-γ1) to the actin cytoskeleton, which was required to bring PLC-γ1 close to its substrate phosphatidylinositol 4,5-bisphosphate, and were reversed by reconstitution of cells with RIAM. Thus, by regulating the localization of PLC-γ1, RIAM plays a central role in TCR signaling and the transcription of target genes.

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