Mechanisms and functions of CRACR2A-L Rab GTPase in vascular endothelial cells

点击翻译按钮获取中文摘要

Thrombus formation (blood clotting) is an essential process to maintain vascular integrity and prevent excessive bleeding after vessel damage. However abnormal thrombi formation leads to blood vessel occlusions and development of atherosclerotic plaques with subsequent hypertension, stroke or ischaemia. Von-Willebrand Factor (vWF)-mediated platelet adhesion is a major regulator of thrombus formation, therefore vWF secretion from endothelial cells is highly regulated. Increased plasma levels of vWF have been proposed as a risk factor for cardiovascular disease, especially in high risk groups such as diabetics. vWF is contained in special storage vesicles called Weibel Palade Bodies (WPBs) which rapidly release their constituents upon stimulation. Agonist induced vWF secretion is a Ca2+-dependent process and is regulated by molecular switches called Rab GTPases. The protein that couples the rise in agonist-induced intracellular Ca2+ to Rab GTPase activation has remained elusive despite being the focus of several research groups. However, we recently identified a novel Rab GTPase expressed in endothelial cells that, unlike the majority of the Rab GTPase family, contains Ca2+ binding domains. This research proposes that the Ca2+ binding Rab GTPase, CRACR2A-L, has important functions and could potentially be offered as a target for novel therapeutics for athero-thrombotic diseases.