López Esther, Gómez-Gordo L, Cantonero Carlos, Bermejo Nuria, Pérez-Gómez Jorge, Granados María P, Salido Gines M, Rosado Dionisio Juan A, Redondo Liberal Pedro C
Department of Physiology (PHYCELL) of the Veterinary Faculty, University of Extremadura, Cáceres, Spain.
Department of Animal Medicine, Veterinary Faculty University of Extremadura, Cáceres, Spain.
Front Physiol. 2018 Mar 23;9:266. doi: 10.3389/fphys.2018.00266. eCollection 2018.
Stanniocalcin 2 (STC2) is a fish protein that controls body Ca and phosphate metabolism. STC2 has also been described in mammals, and as platelet function highly depends on both extracellular and intracellular Ca, we have explored its expression and function in these cells. STC2 mice exhibit shorter tail bleeding time than WT mice. Platelets from STC2-deficient mice showed enhanced aggregation, as well as enhanced Ca mobilization in response to the physiological agonist thrombin (Thr) and the diacylglycerol analog, OAG, a selective activator of the non-capacitative Ca entry channels. Interestingly, platelets from STC2 mice exhibit attenuated interaction between STIM1 and Orai1 in response to Thr, thus suggesting that STC2 is required for Thr-evoked STIM1-Orai1 interaction and the subsequent store-operated Ca entry (SOCE). We have further assessed possible changes in the expression of the most relevant channels involved in non-capacitative Ca entry in platelets. Then, protein expression of Orai3, TRPC3 and TRPC6 were evaluated by Western blotting, and the results revealed that while the expression of Orai3 was enhanced in the STC2-deficient mice, others like TRPC3 and TRPC6 remains almost unaltered. Summarizing, our results provide for the first time evidence for a role of STC2 in platelet physiology through the regulation of agonist-induced Ca entry, which might be mediated by the regulation of Orai3 channel expression.
鲽源钙调蛋白2（STC2）是一种调节机体钙和磷代谢的鱼类蛋白质。在哺乳动物中也发现了STC2，由于血小板功能高度依赖细胞外和细胞内钙，我们研究了STC2在这些细胞中的表达和功能。STC2基因敲除小鼠的尾部出血时间比野生型小鼠短。STC2基因敲除小鼠的血小板表现出更强的聚集能力，以及对生理激动剂凝血酶（Thr）和二酰甘油类似物OAG（非容量性钙内流通道的选择性激活剂）的钙动员增强。有趣的是，STC2基因敲除小鼠的血小板在受到Thr刺激时，STIM1和Orai1之间的相互作用减弱，这表明STC2是Thr诱导的STIM1-Orai1相互作用以及随后的储存性钙内流（SOCE）所必需的。我们进一步评估了血小板中参与非容量性钙内流的最相关通道表达的可能变化。然后，通过蛋白质免疫印迹法评估Orai3、TRPC3和TRPC6的蛋白表达，结果显示，虽然Orai3在STC2基因敲除小鼠中的表达增强，但TRPC3和TRPC6等其他通道的表达几乎没有变化。总之，我们的结果首次证明了STC2通过调节激动剂诱导的钙内流在血小板生理过程中发挥作用，这可能是由Orai3通道表达的调节介导的。
