Ren Qiansheng, Ye Shaojing, Whiteheart Sidney W
Department of Molecular and Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
Curr Opin Hematol. 2008 Sep;15(5):537-41. doi: 10.1097/MOH.0b013e328309ec74.
In response to agonists produced at vascular lesions, platelets release a host of components from their three granules: dense core, alpha, and lysosome. This releasate activates other platelets, promotes wound repair, and initiates inflammatory responses. Although widely accepted, the specific mechanisms underlying platelet secretion are only now coming to light. This review focuses on the core machinery required for platelet secretion.
Proteomic analyses have provided a catalog of the components released from activated platelets. Experiments using a combination of in-vitro secretion assays and knockout mice have led to assignments of both vesicle-soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (v-SNARE) and target membrane SNARE to each of the three secretion events. SNARE knockout mice are also proving to be useful models for probing the role of platelet exocytosis in vivo. Other studies are beginning to identify SNARE regulators, which control when and where SNAREs interact during platelet activation.
A complex set of protein-protein interactions control the membrane fusion events required for the platelet release reaction. SNARE proteins are the core elements but the proteins that control SNARE interactions represent key points at which platelet signaling cascades could affect secretion and thrombosis.
为响应血管损伤部位产生的激动剂,血小板从其三种颗粒(致密核心颗粒、α颗粒和溶酶体)中释放大量成分。这种释放产物可激活其他血小板、促进伤口修复并引发炎症反应。尽管这一观点已被广泛接受,但血小板分泌的具体机制直到现在才逐渐明晰。本综述聚焦于血小板分泌所需的核心机制。
蛋白质组学分析提供了活化血小板释放成分的目录。结合体外分泌测定和基因敲除小鼠的实验已确定了三种分泌事件中每种事件的囊泡可溶性N - 乙基马来酰亚胺敏感融合蛋白附着蛋白受体(v - SNARE)和靶膜SNARE。SNARE基因敲除小鼠也被证明是研究血小板胞吐作用在体内作用的有用模型。其他研究开始鉴定SNARE调节因子,这些调节因子控制血小板激活过程中SNARE相互作用的时间和位置。
一组复杂的蛋白质 - 蛋白质相互作用控制着血小板释放反应所需的膜融合事件。SNARE蛋白是核心元件,但控制SNARE相互作用的蛋白质代表了血小板信号级联反应可能影响分泌和血栓形成的关键点。