RhoG protein regulates glycoprotein VI-Fc receptor γ-chain complex-mediated platelet activation and thrombus formation

Soochong Kim, Carol Dangelmaier, Dheeraj Bhavanasi, Shu Meng, Hong Wang, Lawrence E. Goldfinger, Satya P. Kunapuli

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

We investigated the mechanism of activation and functional role of a hitherto uncharacterized signaling molecule, RhoG, in platelets. We demonstrate for the first time the expression and activation of RhoG in platelets. Platelet aggregation, integrin αIIbβ3 activation, and α-granule and dense granule secretion in response to the glycoprotein VI (GPVI) agonists collagen-related peptide (CRP) and convulxin were significantly inhibited in RhoG-deficient platelets. In contrast, 2-MeSADP- and AYPGKF-induced platelet aggregation and secretion were minimally affected in RhoG-deficient platelets, indicating that the function of RhoG in platelets is GPVI-specific. CRP-induced phosphorylation of Syk, Akt, and ERK, but not SFK (Src family kinase), was significantly reduced in RhoG-deficient platelets. CRP-induced RhoG activation was consistently abolished by a pan-SFK inhibitor but not by Syk or PI3K inhibitors. Interestingly, unlike CRP, platelet aggregation and Syk phosphorylation induced by fucoidan, a CLEC-2 agonist, were unaffected in RhoG-deficient platelets. Finally, RhoG-/-mice had a significant delay in time to thrombotic occlusion in cremaster arterioles compared with wild-type littermates, indicating the important in vivo functional role of RhoG in platelets. Our data demonstrate that RhoG is expressed and activated in platelets, plays an important role in GPVI-Fc receptor y-chain complexmediated platelet activation, and is critical for thrombus formation in vivo.

Original languageEnglish (US)
Pages (from-to)34230-34238
Number of pages9
JournalJournal of Biological Chemistry
Volume288
Issue number47
DOIs
StatePublished - Nov 22 2013

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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