Andrews Robert K, Berndt Michael C
Department of Immunology, Alfred Medical Research & Education Precinct (AMREP), Monash University, Melbourne, Victoria, Australia.
J Clin Invest. 2008 Sep;118(9):3009-11. doi: 10.1172/JCI36883.
The interaction of circulating platelets with the vessel wall involves a process of cell catch and release, regulating cell rolling, skipping, or firm adhesion and leading to thrombus formation in flowing blood. In this regard, the interaction of platelet glycoprotein Ibalpha (GPIbalpha) with its adhesive ligand, vWF, is activated by shear force and critical for platelet adhesion to the vessel wall. In this issue of the JCI, Yago and colleagues show how gain-of-function mutations in the GPIbalpha-binding vWF A1 domain disrupt intramolecular interactions within WT vWF A1 that regulate binding to GPIbalpha and flow-enhanced platelet rolling and adhesion (see the related article beginning on page 3195). Together, these studies reveal molecular mechanisms regulating GPIbalpha-vWF bond formation and platelet adhesion under shear stress.
循环血小板与血管壁的相互作用涉及细胞捕获和释放过程，调节细胞滚动、跳跃或牢固黏附，并导致流动血液中血栓形成。在这方面，血小板糖蛋白Ibalpha（GPIbalpha）与其黏附配体血管性血友病因子（vWF）的相互作用被剪切力激活，对血小板黏附于血管壁至关重要。在本期《临床研究杂志》中，亚戈及其同事展示了GPIbalpha结合的vWF A1结构域中的功能获得性突变如何破坏野生型vWF A1内的分子内相互作用，这些相互作用调节与GPIbalpha的结合以及血流增强的血小板滚动和黏附（见第3195页开始的相关文章）。这些研究共同揭示了在剪切应力下调节GPIbalpha-vWF键形成和血小板黏附的分子机制。
