Department of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon, USA.
Knight Cardiovascular Institute, Oregon Health & Science University, Portland, Oregon, USA.
Small GTPases. 2021 Sep-Nov;12(5-6):440-457. doi: 10.1080/21541248.2021.1878001. Epub 2021 Apr 12.
Platelets are master regulators and effectors of haemostasis with increasingly recognized functions as mediators of inflammation and immune responses. The Rho family of GTPase members Rac1, Cdc42 and RhoA are known to be major components of the intracellular signalling network critical to platelet shape change and morphological dynamics, thus playing a major role in platelet spreading, secretion and thrombus formation. Initially linked to the regulation of actomyosin contraction and lamellipodia formation, recent reports have uncovered non-canonical functions of platelet RhoGTPases in the regulation of reactive oxygen species (ROS), where intrinsically generated ROS modulate platelet function and contribute to thrombus formation. Platelet RhoGTPases orchestrate oxidative processes and cytoskeletal rearrangement in an interconnected manner to regulate intracellular signalling networks underlying platelet activity and thrombus formation. Herein we review our current knowledge of the regulation of platelet ROS generation by RhoGTPases and their relationship with platelet cytoskeletal reorganization, activation and function.
血小板是止血的主要调控因子和效应器，其在炎症和免疫反应中的中介作用也越来越受到重视。Rho 家族 GTPase 成员 Rac1、Cdc42 和 RhoA 是细胞内信号网络的主要组成部分，对血小板形态变化和形态动力学至关重要，因此在血小板扩展、分泌和血栓形成中发挥主要作用。最初与肌动球蛋白收缩和片状伪足形成的调节有关，最近的报道揭示了血小板 RhoGTPase 在调节活性氧 (ROS) 中的非典型功能，其中内在产生的 ROS 调节血小板功能并有助于血栓形成。血小板 RhoGTPases 以相互关联的方式协调氧化过程和细胞骨架重排，以调节血小板活性和血栓形成的细胞内信号网络。本文综述了我们目前对 RhoGTPase 调节血小板 ROS 生成及其与血小板细胞骨架重组、激活和功能关系的认识。
