Wu Jiayu, Heemskerk Johan W M, Baaten Constance C F M J
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands.
Institute for Molecular Cardiovascular Research (IMCAR), University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany.
Front Cardiovasc Med. 2021 Jan 8;7:608391. doi: 10.3389/fcvm.2020.608391. eCollection 2020.
The activities of adhesion and signaling receptors in platelets are controlled by several mechanisms. An important way of regulation is provided by proteolytic cleavage of several of these receptors, leading to either a gain or a loss of platelet function. The proteases involved are of different origins and types: (i) present as precursor in plasma, (ii) secreted into the plasma by activated platelets or other blood cells, or (iii) intracellularly activated and cleaving cytosolic receptor domains. We provide a comprehensive overview of the proteases acting on the platelet membrane. We describe how these are activated, which are their target proteins, and how their proteolytic activity modulates platelet functions. The review focuses on coagulation-related proteases, plasmin, matrix metalloproteinases, ADAM(TS) isoforms, cathepsins, caspases, and calpains. We also describe how the proteolytic activities are determined by different platelet populations in a thrombus and conversely how proteolysis contributes to the formation of such populations.
血小板中黏附受体和信号受体的活性受多种机制控制。其中一种重要的调节方式是通过对这些受体中的几种进行蛋白水解切割，从而导致血小板功能的增强或丧失。所涉及的蛋白酶来源和类型各异：（i）以血浆前体形式存在；（ii）由活化的血小板或其他血细胞分泌到血浆中；或（iii）在细胞内被激活并切割胞质受体结构域。我们对作用于血小板膜的蛋白酶进行了全面概述。我们描述了这些蛋白酶是如何被激活的，它们的靶蛋白是什么，以及它们的蛋白水解活性如何调节血小板功能。本综述重点关注与凝血相关的蛋白酶、纤溶酶、基质金属蛋白酶、ADAM（TS）同工型、组织蛋白酶、半胱天冬酶和钙蛋白酶。我们还描述了血栓中不同血小板群体如何决定蛋白水解活性，以及相反地，蛋白水解如何促成这些群体的形成。
