ESCRT复合体在细胞质膜损伤修复中的功能

The Function of ESCRT Complex in Plasma Membrane Repair

细胞膜损伤在骨骼肌、血管内皮及胃肠道上皮等组织较为常见,及时有效的细胞膜修复(plasma membrane repair,PMR)能够保证细胞存活,反之,细胞则可能“死亡”。PMR由许多“修补匠”协同完成,它们分工明确且呈现出一定的时序特点。转运必需内体分选复合体(endosomal sorting complex required for transport,ESCRT)是近年来研究发现的在细胞膜损伤修复中发挥关键作用的“修补匠”,其由ESCRT-0、ESCRT-Ⅰ、ESCRT-Ⅱ、ESCRT-Ⅲ、Vps4-Vta1及ALIX组成,主要参与胞外出芽(budding)和多囊泡体(multivesicular body,MVB)形成两种修复途径。本文详细综述了ESCRT系统介导细胞膜损伤修复的可能机制,以期为细胞膜损伤的治疗靶点筛选及促恢复手段创新提供理论依据。

Plasma membrane disruptions have been documented under physiological conditions in lots of mechanically active tissues,such as in skeletal muscle,the stratified epithelium that covers our body,the endothelia that line our blood vessels,the epithelial barrier of our gastrointestinal tract.Timely and effective plasma membrane repair(PMR)mechanisms have evolved to rapidly reseal a membrane breach to ensure cell survival.Otherwise,these membrane disruption events initiate a“death cascade”.PMR is coordinated by many“tinkerers”,which have a clear division of labor and show certain timing characteristics.The endosomal sorting complexes required for transport(ESCRT)is the“tinkerer”found recently who plays a key role in the repair of plasma membrane disruptions.It is composed of ESCRT-0,ESCRT-Ⅰ,ESCRT-Ⅱ,ESCRT-Ⅲ,VPS4-VTA1 and ALIX,which take part in the budding and the formation of multivesicular body(MVB).This paper reviews two repair methods mediated by ESCRT system with budding and the formation of MVB.The function of ESCRT complex in plasma membrane repair can improve membrane disruptions,which is able to be used as an effective prevention and treatment strategy for cancer,Alzheimer’s disease,muscle injury and muscular dystrophy.