Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion
Glycoprotein Ib-IX-V Complex Transmits Cytoskeletal Forces That Enhance Platelet Adhesion
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DOI：
10.1016/j.bpj.2016.06.023
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发表时间：
2016-08-09
影响因子：
3.4
通讯作者：
Sniadecki, Nathan J.
中科院分区：
文献类型：
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作者：
Feghhi, Shirin;Munday, Adam D.;Sniadecki, Nathan J.
血小板通过高度特化的表面受体糖蛋白（GP）Ib-IX-V复合物与伤口部位暴露的血管基质结合，该复合物识别基质中的血管性血友病因子（VWF）。GPIb-IX-V是一种捕获键，因为它在施加力时变得更加稳定。在附着到伤口部位后，血小板产生细胞骨架力以压缩和加强止血塞。在这里，我们评估了GPIb-IX-V复合物在细胞骨架力传递中的作用。我们使用柔性硅纳米柱阵列来测量VWF上单个血小板的收缩性。我们发现，一个显着的比例的细胞骨架力通过GPIb-IX-V传输到VWF，一个意想不到的发现，鉴于广泛持有的概念，血小板力是通过其整合素完全传输。特别是，我们发现GPIb α和VWF的A1结构域之间的相互作用介导了这种力的传递。我们还表明，GPIb α和细丝蛋白A之间的结合相互作用参与力的传递。此外，我们的研究表明，当没有外力时，通过GPib alpha作用的细胞骨架力参与维持血小板粘附。因此，GPIb-IX-V/VWF键能够传递力，并通过捕获键机制使用该力来加强键。这一发现扩展了我们对血小板如何附着在血管损伤部位的理解，描述了一种新的机制，据我们所知，GPIb-IX-V/VWF的捕获键可以由细胞骨架张力产生的内力支持。
Platelets bind to exposed vascular matrix at a wound site through a highly specialized surface receptor, glycoprotein (GP) Ib-IX-V complex, which recognizes von Willebrand factor (VWF) in the matrix. GPIb-IX-V is a catch bond for it becomes more stable as force is applied to it. After attaching to the wound site, platelets generate cytoskeletal forces to compact and reinforce the hemostatic plug. Here, we evaluated the role of the GPIb-IX-V complex in the transmission of cytoskeletal forces. We used arrays of flexible, silicone nanoposts to measure the contractility of individual platelets on VWF. We found that a significant proportion of cytoskeletal forces were transmitted to VWF through GPIb-IX-V, an unexpected finding given the widely held notion that platelet forces are transmitted exclusively through its integrins. In particular, we found that the interaction between GPIb alpha and the A1 domain of VWF mediates this force transmission. We also demonstrate that the binding interaction between GPIb alpha and filamin A is involved in force transmission. Furthermore, our studies suggest that cytoskeletal forces acting through GPIb alpha are involved in maintaining platelet adhesion when external forces are absent. Thus, the GPIb-IX-V/VWF bond is able to transmit force, and uses this force to strengthen the bond through a catch-bond mechanism. This finding expands our understanding of how platelets attach to sites of vascular injury, describing a new, to the best of our knowledge, mechanism in which the catch bonds of GPIb-IX-V/VWF can be supported by internal forces produced by cytoskeletal tension.