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Sci. Signal., 1 December 2009
Vol. 2, Issue 99, p. ra79
[DOI: 10.1126/scisignal.2000409]

RESEARCH ARTICLES

RIAM Regulates the Cytoskeletal Distribution and Activation of PLC-{gamma}1 in T Cells

Nikolaos Patsoukis1, Esther M. Lafuente2*, Paul Meraner3, Jin sub Kim1, David Dombkowski4, Lequn Li1, and Vassiliki A. Boussiotis1{dagger}

1 Department of Hematology-Oncology and Cancer Biology, Beth Israel Deaconess Medical Center, Center for Life Sciences, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
2 Transplantation Biology Research Center, Massachusetts General Hospital, Boston, MA 02129, USA.
3 Center for Blood Research/Infectious Disease Institute, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
4 Department of Pathology, Massachusetts General Hospital, Boston, MA 02129, USA.

* Present address: Departamento de Microbiologica I, Area Immunologia Facultad de Medicina Pabellon V, planta 4, despacho 10, Universidad Complutense de Madrid, Av Complutense s/n, 28040 Madrid, Spain.

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–{gamma}1 (PLC-{gamma}1) to the actin cytoskeleton, which was required to bring PLC-{gamma}1 close to its substrate phosphatidylinositol 4,5-bisphosphate, and were reversed by reconstitution of cells with RIAM. Thus, by regulating the localization of PLC-{gamma}1, RIAM plays a central role in TCR signaling and the transcription of target genes.

{dagger} To whom correspondence should be addressed. E-mail: vboussio{at}bidmc.harvard.edu

Citation: N. Patsoukis, E. M. Lafuente, P. Meraner, J. s. Kim, D. Dombkowski, L. Li, V. A. Boussiotis, RIAM Regulates the Cytoskeletal Distribution and Activation of PLC-{gamma}1 in T Cells. Sci. Signal. 2, ra79 (2009).

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