Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


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


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}

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).

Read the Full Text

Focal adhesion disassembly is regulated by a RIAM to MEK-1 pathway.
G. P. Colo, P. Hernandez-Varas, J. Lock, R. A. Bartolome, N. Arellano-Sanchez, S. Stromblad, and J. Teixido (2012)
J. Cell Sci. 125, 5338-5352
   Abstract »    Full Text »    PDF »
Rap1-GTP-interacting Adaptor Molecule (RIAM) Protein Controls Invasion and Growth of Melanoma Cells.
P. Hernandez-Varas, G. P. Colo, R. A. Bartolome, A. Paterson, I. Medrano-Fernandez, N. Arellano-Sanchez, C. Cabanas, P. Sanchez-Mateos, E. M. Lafuente, V. A. Boussiotis, et al. (2011)
J. Biol. Chem. 286, 18492-18504
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882