STIM and Orai in platelet function

Physiological platelet activation and thrombus formation are essential to stop bleeding in case of vascular injury, whereas inadequate triggering of the same process in diseased vessels can lead to fatal thromboembolism and tissue ischemia of vital organs. A central step in platelet activation is agonist-induced elevation of the intracellular Ca2+ concentration. This happens on the one hand through the release of Ca2+ from intracellular stores and on the other hand through Ca2+ influx from the extracellular space. In platelets, the major Ca2+ influx pathway is the so-called store operated Ca2+ entry (SOCE), induced by store depletion. Studies in the last five years discovered the molecular background of platelet SOCE. Stromal interaction molecule 1 (STIM1) and Orai1, two so far unknown molecules, got in the focus of research. STIM1 was found to be the Ca2+ sensor in the endoplasmic reticulum (ER) membrane, whereas Orai1 was identified as the major store operated Ca2+ (SOC) channel in the plasma membrane. These two molecules and their role in platelet function and thrombus formation are the topic of the present review with a special focus on apoptosis and apoptosis-like processes in platelet physiology. (C) 2011 Published by Elsevier Ltd.