RIAM regulates the cytoskeletal distribution and activation of PLC-gamma1 in T cells.
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 (Ca(2+)), 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-gamma1 (PLC-gamma1) to the actin cytoskeleton, which was required to bring PLC-gamma1 close to its substrate phosphatidylinositol 4,5-bisphosphate, and were reversed by reconstitution of cells with RIAM. Thus, by regulating the localization of PLC-gamma1, RIAM plays a central role in TCR signaling and the transcription of target genes.
Patsoukis
Nikolaos
N
Department of Hematology-Oncology and Cancer Biology, Beth Israel Deaconess Medical Center, Center for Life Sciences, Harvard Medical School, Boston, MA 02215, USA.
Lafuente
Esther M
EM
Meraner
Paul
P
Kim
Jin sub
Js
Dombkowski
David
D
Li
Lequn
L
Boussiotis
Vassiliki A
VA
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000201:enzymology*; D006801:Humans; D019169:Jurkat Cells; D008565:Membrane Proteins / Q000502:physiology*; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism*; D021381:Protein Transport; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
C493340:APBB1IP protein, human; D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D011948:Receptors, Antigen, T-Cell; D051966:Phospholipase C gamma