Department of Physiology, Cell Physiology Research Group, University of Extremadura, 10003, Caceres, Spain.
Curr Mol Med. 2012 Dec;12(10):1319-28. doi: 10.2174/156652412803833616.
Recent studies have demonstrated that mammalian homologues of Drosophila transient receptor potential (TRP) channels are widely expressed in human platelets. Occupation of G protein-coupled receptors by agonists results in activation of these channels, which results in Na+ and Ca2+ entry. Canonical or classic TRP (TRPC) family members have been reported to associate with different Ca2+-handling proteins, including the type II inositol 1,4,5-trisphosphate receptor, the endoplasmic reticulum Ca2+ sensor STIM1 (STromal Interaction Molecule-1) or the Ca2+ permeable channel Orai1. The dynamic interaction of TRPC channels with the above mentioned proteins has been found to be important for both store-operated and capacitative Ca2+ entry, as well as for non-capacitative Ca2+ influx. The former is a major mechanism for Ca2+ entry in human platelets. This mechanism, activated by a reduction in the concentration of free Ca2+ in the intracellular stores, results in the formation of signaling complexes involving STIM proteins, Orai1, Orai2, TRPC1 and TRPC6. There is a growing body of evidence supporting that Ca2+ signaling dysfunction plays an important role in the pathogenesis of several platelet-linked disorders, including those associated to type 2 diabetes mellitus. Abnormal Ca2+ signals in response to physiological agonists have been associated to platelet hyperactivity. The expression of several TRPCs, STIM1 and Orai1, as well as their interaction, has been reported to be altered in platelets from type 2 diabetic patients, which results in attenuated capacitative Ca2+ entry but enhanced non-capacitative Ca2+ influx; thus suggesting a role for Ca2+ handling proteins, including TRPs, in the pathomechanism of diabetic complications.
最近的研究表明，果蝇瞬时受体电位（TRP）通道的哺乳动物同源物广泛表达于人血小板中。激动剂占据 G 蛋白偶联受体可激活这些通道，导致 Na+和 Ca2+内流。已经报道经典或经典 TRP（TRPC）家族成员与不同的 Ca2+处理蛋白相关，包括 II 型肌醇 1,4,5-三磷酸受体、内质网 Ca2+传感器 STIM1（基质相互作用分子-1）或 Ca2+通透通道 Orai1。已经发现 TRPC 通道与上述蛋白的动态相互作用对于储存操作和电容性 Ca2+内流以及非电容性 Ca2+内流都很重要。前者是人类血小板中 Ca2+内流的主要机制。这种机制由细胞内储存中游离 Ca2+浓度的降低激活，导致涉及 STIM 蛋白、Orai1、Orai2、TRPC1 和 TRPC6 的信号复合物的形成。越来越多的证据支持 Ca2+信号功能障碍在几种与血小板相关的疾病的发病机制中起着重要作用，包括与 2 型糖尿病相关的疾病。对生理激动剂的异常 Ca2+信号与血小板过度活跃有关。已经报道，2 型糖尿病患者的血小板中几种 TRPCs、STIM1 和 Orai1 的表达及其相互作用发生改变，导致电容性 Ca2+内流减弱但非电容性 Ca2+内流增强；因此，Ca2+处理蛋白（包括 TRP）在糖尿病并发症的发病机制中起作用。
