肌肉细胞内质网-质膜互作与CRAC信号通路

ER-PM contacts and CRAC signaling in muscle cells

细胞通过内质网(endoplasmic reticulum, ER)-质膜(plasma membrane, PM)之间的膜接触点(简称为ER-PM连接区)进行脂类传递和钙信号转导.该连接区占据神经元胞体处质膜表面积的12%,且是肌肉细胞兴奋-收缩偶联所必须的.当前对神经元中该区的动态特征及生物学功能还所知甚少,对兴奋性细胞中该区中的蛋白质图谱也了解得比较有限.而作为连接区内介导ER-PM互作的蛋白质机器,钙池释放钙通道钙释放激活钙(calcium releaseactivated calcium, CRAC)通道在兴奋性细胞中的调控、生理和病理作用也有待进一步阐明.近年来,超分辨成像,光遗传学技术及蛋白邻近标记技术的出现,为回答这些问题提供了有力的工具.本文因而总结了ER-PM连接区的动态观测与蛋白质组学鉴定,及肌肉细胞的CRAC通路等研究方向上的最新进展,并对后续相关研究进行了初步的展望.

Membrane contact sites(MCS) between endoplasmic reticulum(ER) and plasma membrane(PM), named ER-PM junctions, are crucial for lipid transfer and calcium signaling. ER-PM junction occupies 12% of PM in neurons and is essential for excitationcontraction coupling(ECC) in muscle cells. Currently, the dynamics and biological function of ER-PM junctions in neurons still remain elusive, and known information of proteomics within this region is also limited. The regulation and physiological/pathological function of calcium release-activated calcium(CRAC) channels, well established tethers that mediate ER-PM contacts, are waiting to be further unraveled. Recent advances in super-resolution imaging, optogenetic technology and proximity labeling provide possible solutions to address the aforementioned scientific questions. This review summarized recent advances in understanding the dynamics and proteomics of ER-PM junctions as well as CRAC signaling in muscle cells, and further directions of related research was briefly discussed.