星形胶质细胞调节性容积减小(RVD)的关键膜蛋白研究进展  

Key Players in Astrocyte Regulatory Volume Reduction(RVD):VRAC and Aquaporin

作　　者：周佐邑 高嘉琪 高凯[2] 龚艳君[1] 于常海[3] ZHOU Zuo-Yi;GAO Jia-Qi;GAO Kai;GONG Yan-Jun;YU Albert Cheung Hoi(Department of Cardiology,Peking University First Hospital,Beijing 100034,China;Department of Pediatrics,Peking University First Hospital,Beijing 100034,China;Neuroscience Research Institute,School of Basic Medical Sciences,Peking University Health Science Center,Beijing 100191,China;Department of Gastroenterology,Peking University Third Hospital,Beijing 100191,China)

机构地区：[1]北京大学第一医院心血管内科,北京100034 [2]北京大学第一医院儿科,北京100034 [3]北京大学基础医学院,神经科学研究所,北京100191 [4]北京大学第三医院消化内科,北京100191

出　　处：《生物化学与生物物理进展》2022年第11期2165-2171,共7页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(81471253,82171435);国家自然科学基金创新研究群体科学基金(81221002);北京市自然科学基金(7091004)资助项目。

摘　　要：星形胶质细胞承担着维持脑部内环境稳态的重要功能,包括维持脑的水电解质平衡。然而,在缺血性脑卒中等多种疾病中,星形胶质细胞会首先出现明显的细胞水肿,进而促进脑水肿的发生,加重脑损伤。调节性容积减小(RVD)是星形胶质细胞面对水肿时快速减小自身部分容积的代偿反应。最新研究进展发现,水通道蛋白(AQP)和体积调节性阴离子通道(VRAC)是RVD过程的关键参与者。VRAC是LRRC8家族成员构成的异多聚体,星形胶质细胞水肿时,VRAC激活,介导阴离子和有机渗透性物质快速向细胞外转运,是RVD的主要驱动力。AQP是一种6次跨膜蛋白,具有选择性的双向水通道,是星形胶质细胞快速水肿的结构基础,同时也是RVD过程中水转移至胞外的“快速通道”。进一步了解VRAC和AQP的结构、功能及其在RVD中发挥的作用,有助于最终解析星形胶质细胞RVD的发生机制并为脑水肿的治疗提供潜在靶点。Astrocytes play important roles in maintaining the homeostasis of brain,including the maintenance of brain’s water balance.However,under various diseases such as ischemic stroke,astrocytes are the first to show significant cellular edema,which in turn promotes the development of cerebral edema and aggravates brain injury.Regulatory volume reduction(RVD)is a compensatory response of astrocytes to rapidly reduce part of their volume in the face of fast swelling.Recent advances have revealed that volume-regulated anion channel(VRAC)and aquaporin(AQP)are key players in the RVD process.VRAC is a heteromers composed of members of the LRRC8 family.During astrocyte fast swelling,VRAC is activated and mediates the rapid transport of anions and organic osmolytes to extracellular space,which is the main driver of RVD.AQP,a six-transmembrane protein,is a selective bidirectional water channel,which is the structural basis for rapid cellular edema in astrocytes and is also the"fast track"for water transport to the extracellular compartment during RVD.Further understanding of the structure and function of VRAC and AQP and their roles in RVD will help to finally understand the mechanism of astrocyte RVD and provide potential targets for the treatment of brain edema.

关 键 词：水通道蛋白 体积调节性阴离子通道 调节性容积减小 星形胶质细胞 脑水肿 

分 类 号：Q421[生物学—神经生物学] Q51[生物学—生理学]