ERM蛋白在微血管内皮细胞通透性调控中的研究进展

埃兹蛋白(Ezrin)/根蛋白(Radixin)/膜突蛋白(Moesin)(ERM)是细胞膜与胞内骨架的连接蛋白,具有高度同源性。细胞外刺激因子可通过多种信号通路磷酸化ERM蛋白,使细胞骨架重构,从而调控微血管内皮细胞通透性,在感染、炎症、代谢异常等病理过程中发挥作用。ERM功能调节的一个重要环节就是其羧基末端苏氨酸残基磷酸化后引起ERM构象的改变,暴露的羧基末端尾部的肌动蛋白(actin)-细胞骨架结合位点;故通过ERM的桥接作用,可将肌动蛋白微丝与细胞膜相连,使血管内皮细胞屏障功能发生变化。目前已知能使ERM磷酸化的激酶有蛋白激酶C(PKC)、促分裂原活化蛋白激酶(MAPK)、Rho相关激酶(ROCK),分别通过p38-MAPK、Rho/ROCK、PKC信号通路参与微血管内皮屏障功能的调控。本文旨在阐述ERM及其相关信号通路在微血管内皮细胞通透性调控中发挥的作用。

Progress on ERMProteins in Regulation of Microvascular Endothelial Permeability

The ezrin-radixin-moesin (ERM) family with high homology serve as membrane-cytoskeletal linker proteins. Phosphorylation of ERM proteins via various pathways by extracellular stimulation, leads to cytoskeleton remodeling and then regulate microvascular endothelial permeability, which play an important role in the pathological process, such as infection, inflammation, and metabolic disorder. Phosphorylation of the threonine residues of its carboxyl terminal induces conformation change of ERM, which leads to the exposure of its binding site to actin cytoskeleton. Thus, the actin filaments can be connected with the membrane by ERM and the vascular endothelial barrier function will be affected. It has been reported that ERM can be phosphorylated by kinase protein kinase C (PKC), mitogen activated protein kinase (MAPK) and Rho related kinase (ROCK) via p38-MAPK, Rho/ROCK, PKC signaling pathway, respectively, which are involved in modulation of microvascular endothelial barrier. This review aims at clarifying the effect of ERMand its related signaling pathways in microvascular endothelial permeability regulation.