Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada; Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, BC, Canada.
Centre for Blood Research, University of British Columbia, Vancouver, BC, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada.
Cell Signal. 2024 Dec;124:111433. doi: 10.1016/j.cellsig.2024.111433. Epub 2024 Sep 24.
Upon activation by vascular injury or extracellular agonists, platelets undergo rapid change shape, a process regulated by the actin cytoskeleton and accessory proteins. Platelet shape change is accompanied by the secretion of hemostatic factors and immunomodulatory cytokines from their intracellular granules, as well as the release of microvesicles (MVs) containing pro-inflammatory cytokines and procoagulant phosphatidylserine (PS). However, the role of actin dynamics in MV generation remains unclear. In this study, we found that blocking actin polymerization with cytochalasin D attenuated the release of PS-positive MVs in human platelets stimulated by thrombin or the calcium ionophore A23187. The actin-severing protein gelsolin (Gsn) facilitates normal actin filament turnover in activated platelets. Platelets from Gsn-deficient (Gsn) mice showed reduced MV release compared to platelets from control mice. These findings indicate that the proper dynamics of the actin cytoskeleton are essential for MV generation in platelets, which has implications for their pro-inflammatory and procoagulant functions.
在血管损伤或细胞外激动剂激活后，血小板发生快速的形态变化，这一过程受肌动蛋白细胞骨架和辅助蛋白调节。血小板形态变化伴随着其细胞内颗粒中止血因子和免疫调节细胞因子的分泌，以及含有促炎细胞因子和促凝血磷脂酰丝氨酸（PS）的微泡（MV）的释放。然而，肌动蛋白动力学在 MV 生成中的作用仍不清楚。在这项研究中，我们发现，细胞松弛素 D 阻断肌动蛋白聚合可减弱凝血酶或钙离子载体 A23187 刺激的人血小板中 PS 阳性 MV 的释放。肌动蛋白切割蛋白凝胶蛋白（Gsn）促进激活血小板中正常的肌动蛋白丝周转。与来自对照小鼠的血小板相比，来自 Gsn 缺陷（Gsn）小鼠的血小板释放的 MV 减少。这些发现表明，肌动蛋白细胞骨架的适当动力学对于血小板中 MV 的生成是必不可少的，这对其促炎和促凝血功能有影响。
