Bergmeier W, Stefanini L
Cardeza Foundation and Department of Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
J Thromb Haemost. 2009 Jul;7 Suppl 1:187-90. doi: 10.1111/j.1538-7836.2009.03379.x.
A rise in the intracellular calcium (Ca2+) concentration is a major component of the signaling mechanisms regulating platelet function in thrombosis and hemostasis. Previous studies, however, failed to identify many key molecules regulating Ca2+ signaling in platelets. Here, we review recent findings, which identified CalDAG-GEFI as a critical Ca2+ sensor that links increases in intracellular Ca2+ to integrin activation, TxA2 formation, and granule release in stimulated platelets. Furthermore, we summarize work that lead to the discovery of STIM1 and Orai1 as key regulators of store-operated calcium entry (SOCE) in platelets. A short discussion on the usefulness of each molecule as a potential new target for antiplatelet therapy is included.
细胞内钙(Ca2+)浓度的升高是血栓形成和止血过程中调节血小板功能的信号传导机制的主要组成部分。然而,以往的研究未能确定许多调节血小板中Ca2+信号传导的关键分子。在此,我们综述了最近的研究发现,这些发现确定了CalDAG-GEFI作为一种关键的Ca2+传感器,它将细胞内Ca2+的增加与整合素激活、血栓素A2(TxA2)形成以及刺激的血小板中的颗粒释放联系起来。此外,我们总结了导致发现STIM1和Orai1作为血小板中储存式钙内流(SOCE)关键调节因子的研究工作。还包括对每个分子作为抗血小板治疗潜在新靶点的有用性的简短讨论。