Regulation of Platelet Function by Orai, STIM and TRP

Rosado J. (eds).Agonist-induced changes in cytosolic Ca2+ concentration ([Ca2+]c) are central events in platelet physiology. A major mechanism supporting agonist-induced Ca2+ signals is store-operated Ca2+ entry (SOCE), where the Ca2+ sensor STIM1 and the channels of the Orai family, as well as TRPC members are the key elements. STIM1-dependent SOCE plays a major role in collagen-stimulated Ca2+ signaling, phosphatidylserine exposure and thrombin generation. Furthermore, studies involving Orai1 gain-of-function mutants and platelets from Orai1-deficient mice have revealed the importance of this channel in thrombosis and hemostasis to those found in STIM1-deficient mice indicating that SOCE might play a prominent role in thrombus formation. Moreover, increase in TRPC6 expression might lead to thrombosis in humans. The role of STIM1, Orai1 and TRPCs, and thus SOCE, in thrombus formation, suggests that therapies directed against SOCE and targeting these molecules during cardiovascular and cerebrovascular events could significantly improve traditional anti-thrombotic treatments.This work was supported by MINECO (Grants BFU2013-45564-C2-1-P and BFU2013-45564-C2-2-P) and Junta de Extremadura-FEDER (GR15029). A. B-E is supported from UPF “MINECO – Plan Nacional de I+D+i(2008-2012) – SAF 2012-38140”.Peer reviewe