Thomas Steven G, Calaminus Simon D J, Auger Jocelyn M, Watson Stephen P, Machesky Laura M
School of Biosciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
BMC Cell Biol. 2007 Nov 9;8:46. doi: 10.1186/1471-2121-8-46.
The platelet cytoskeleton mediates the dramatic change in platelet morphology that takes place upon activation and stabilizes thrombus formation. The Arp2/3 complex plays a vital role in these processes, providing the protrusive force for lamellipodia formation. The Arp2/3 complex is highly regulated by a number of actin-binding proteins including the haematopoietic-specific protein HS1 and its homologue cortactin. The present study investigates the role of HS1 in platelets using HS1-/- mice.
The present results demonstrate that HS1 is not required for platelet activation, shape change or aggregation. Platelets from HS1-/- mice spread normally on a variety of adhesion proteins and have normal F-actin and Arp2/3 complex distributions. Clot retraction, an actin-dependent process, is also normal in these mice. Platelet aggregation and secretion is indistinguishable between knock out and littermates and there is no increase in bleeding using the tail bleeding assay.
This study concludes that HS1 does not play a major role in platelet function. It is possible that a role for HS1 is masked by the presence of cortactin.
血小板细胞骨架介导血小板激活时发生的显著形态变化，并稳定血栓形成。Arp2/3复合体在这些过程中起着至关重要的作用，为片状伪足形成提供突出力。Arp2/3复合体受到多种肌动蛋白结合蛋白的高度调控，包括造血特异性蛋白HS1及其同源物皮层肌动蛋白。本研究使用HS1基因敲除小鼠研究HS1在血小板中的作用。
目前的结果表明，血小板激活、形状改变或聚集不需要HS1。HS1基因敲除小鼠的血小板能在多种黏附蛋白上正常铺展，并且具有正常的F-肌动蛋白和Arp2/3复合体分布。这些小鼠的血块回缩（一个肌动蛋白依赖性过程）也正常。基因敲除小鼠和同窝出生小鼠之间的血小板聚集和分泌没有差异，并且使用尾部出血试验检测未发现出血增加。
本研究得出结论，HS1在血小板功能中不发挥主要作用。HS1的作用可能被皮层肌动蛋白的存在所掩盖。
