Naß Johannes, Terglane Julian, Gerke Volker
Centre for Molecular Biology of Inflammation, Institute of Medical Biochemistry, University of Muenster, Muenster, Germany.
Front Cell Dev Biol. 2021 Dec 16;9:813995. doi: 10.3389/fcell.2021.813995. eCollection 2021.
Vascular endothelial cells produce and release compounds regulating vascular tone, blood vessel growth and differentiation, plasma composition, coagulation and fibrinolysis, and also engage in interactions with blood cells thereby controlling hemostasis and acute inflammatory reactions. These interactions have to be tightly regulated to guarantee smooth blood flow in normal physiology, but also allow specific and often local responses to blood vessel injury and infectious or inflammatory insults. To cope with these challenges, endothelial cells have the remarkable capability of rapidly changing their surface properties from non-adhesive (supporting unrestricted blood flow) to adhesive (capturing circulating blood cells). This is brought about by the evoked secretion of major adhesion receptors for platelets (von-Willebrand factor, VWF) and leukocytes (P-selectin) which are stored in a ready-to-be-used form in specialized secretory granules, the Weibel-Palade bodies (WPB). WPB are unique, lysosome related organelles that form at the trans-Golgi network and further mature by receiving material from the endolysosomal system. Failure to produce correctly matured VWF and release it through regulated WPB exocytosis results in pathologies, most importantly von-Willebrand disease, the most common inherited blood clotting disorder. The biogenesis of WPB, their intracellular motility and their fusion with the plasma membrane are regulated by a complex interplay of proteins and lipids, involving Rab proteins and their effectors, cytoskeletal components as well as membrane tethering and fusion machineries. This review will discuss aspects of WPB biogenesis, trafficking and exocytosis focussing on recent findings describing factors contributing to WPB maturation, WPB-actin interactions and WPB-plasma membrane tethering and fusion.
血管内皮细胞产生并释放调节血管张力、血管生长与分化、血浆成分、凝血和纤溶的化合物，还与血细胞相互作用，从而控制止血和急性炎症反应。这些相互作用必须受到严格调控，以确保正常生理状态下的血流顺畅，同时也允许对血管损伤以及感染或炎症刺激做出特定且往往是局部的反应。为应对这些挑战，内皮细胞具有显著的能力，能够迅速改变其表面特性，从不粘附状态（支持无限制的血流）转变为粘附状态（捕获循环血细胞）。这是通过诱导分泌血小板主要粘附受体（血管性血友病因子，VWF）和白细胞主要粘附受体（P-选择素）实现的，这些受体以 ready-to-be-used 的形式储存在特殊的分泌颗粒——魏尔-帕拉德小体（WPB）中。WPB 是独特的、与溶酶体相关的细胞器，在反式高尔基体网络形成，并通过从内溶酶体系统接收物质进一步成熟。无法产生正确成熟的 VWF 并通过受调控的 WPB 胞吐作用释放它会导致疾病，最重要的是血管性血友病，这是最常见的遗传性凝血障碍。WPB 的生物发生、其在细胞内的运动以及与质膜的融合受到蛋白质和脂质复杂相互作用的调控，涉及 Rab 蛋白及其效应器、细胞骨架成分以及膜拴系和融合机制。本综述将讨论 WPB 生物发生、运输和胞吐作用的各个方面，重点关注描述有助于 WPB 成熟、WPB-肌动蛋白相互作用以及 WPB-质膜拴系和融合的因素的最新研究结果。
