Open Access
Article
STIM and Orai in hemostasis and thrombosis
Attila Braun1,Timo Vogtle1,David Varga-Szabo1,Bernhard Nieswandt1
1
University of Wurzburg, Chair of Vascular Medicine, University Hospital and Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, Germany
DOI: 10.2741/3844 Volume 16 Issue 6, pp.2144-2160
Published: 01 June 2011
Abstract

At sites of vascular injury, platelets rapidly adhere to the exposed subendothelial extracellular matrix, become activated and, together with the coagulation system, form a plug that seals the lesion. This process is essential to prevent blood loss, however, under pathological conditions it may lead to vessel occlusion. Agonist-induced elevation of intracellular Ca(2+) levels is essential for platelet activation. It occurs through two different mechanisms: Ca(2+) release from internal stores, involving phospholipase C (PLC)-dependent generation of inositol-1,4,5-trisphosphate (IP3) and activation of IP3 sensitive channels in the store membrane, and Ca(2+) influx across the plasma membrane. Store operated Ca(2+) entry (SOCE), triggered by store depletion, is the main influx pathway for extracellular Ca(2+) in platelets, but the molecular mechanism underlying this pathway has long remained elusive. In the last years, however, the Ca(2+) sensor stromal interaction molecule 1 (STIM1) and the channel protein Orai1 emerged as the key players in platelet SOCE. This review summarizes the current knowledge about the role of these proteins in platelet physiology and thrombus formation and discusses their suitability as antithrombotic targets.

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Attila Braun, Timo Vogtle, David Varga-Szabo, Bernhard Nieswandt. STIM and Orai in hemostasis and thrombosis. Frontiers in Bioscience-Landmark. 2011. 16(6); 2144-2160.