Regulation of Platelet Function by Orai, STIM and TRP
Regulation of Platelet Function by Orai, STIM and TRP
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DOI：
10.1007/978-3-319-26974-0_8
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发表时间：
2016-01-01
期刊：
影响因子：
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通讯作者：
Rosado, Juan A.
中科院分区：
文献类型：
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作者：
Berna-Erro, Alejandro;Jardin, Isaac;Rosado, Juan A.
激动剂诱导的胞质Ca 2+浓度（[Ca 2 +]（c））的变化是血小板生理学的中心事件。支持激动剂诱导的Ca 2+信号的主要机制是钙库操纵的Ca 2+进入（SOCE），其中Ca 2+传感器STIM 1和奥赖家族的通道以及TRPC成员是关键元件。STIM1依赖性SOCE在胶原刺激的Ca2+信号传导、磷脂酰丝氨酸暴露和凝血酶生成中起主要作用。此外，涉及Orai1功能获得性突变体和Orai1缺陷小鼠血小板的研究揭示了该通道在血栓形成和止血中的重要性，这表明SOCE可能在血栓形成中起重要作用。此外，TRPC 6表达的增加可能导致人类血栓形成。STIM 1、Orai 1和TRPC以及SOCE在血栓形成中的作用表明，在心脑血管事件期间针对SOCE并靶向这些分子的治疗可以显著改善传统的抗血栓形成治疗。
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.