a Institute of Cardiovascular Sciences, College of Medical and Dental Sciences , University of Birmingham , Birmingham , UK.
b Department of Biochemistry , Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht , Maastricht , The Netherlands.
Platelets. 2019;30(3):281-289. doi: 10.1080/09537104.2018.1508649. Epub 2018 Aug 15.
GPVI is the major signalling receptor for collagen on platelets. Dimerization of GPVI is required for collagen binding and initiation of signalling through the associated FcR-γ chain. Recently, fibrin and fibrinogen have been identified as ligands for GPVI and shown to induce signalling in support of thrombus formation and stabilization. Contrasting observations have been reported on whether fibrin binds to monomeric or dimeric GPVI, or to neither form. In this article, we discuss reasons for the contradictory results and how to reconcile these. We conclude that a lack of structural knowledge regarding the GPVI constructs that are being used, along with the use of non-standardized reagents, might be the main cause of the discrepant results. This article aims to highlight some of the key areas that need to be addressed.
GPVI 是血小板上胶原蛋白的主要信号受体。GPVI 的二聚化对于胶原结合和通过相关的 FcR-γ 链启动信号转导是必需的。最近,纤维蛋白和纤维蛋白原已被确定为 GPVI 的配体,并被证明可诱导支持血栓形成和稳定的信号转导。关于纤维蛋白是结合单体 GPVI、二聚体 GPVI 还是两者都不结合,已经有相互矛盾的观察结果报道。在本文中,我们讨论了产生这些矛盾结果的原因,以及如何调和这些结果。我们得出的结论是,缺乏关于正在使用的 GPVI 结构的结构知识,以及使用非标准化试剂,可能是导致结果不一致的主要原因。本文旨在强调需要解决的一些关键领域。