Store-Operated Calcium Entry Mediated by ORAI and STIM
Store-Operated Calcium Entry Mediated by ORAI and STIM
复制标题
由 ORAI 和 STIM 介导的商店操作的钙输入。
DOI：
10.1002/cphy.c170031
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发表时间：
2018-07-01
影响因子：
5.8
通讯作者：
Zhou, Yubin
中科院分区：
文献类型：
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作者：
Nguyen, Nhung T.;Han, Weidong;Zhou, Yubin
由奥赖和基质相互作用分子（STIM）组成的钙释放激活钙（CRAC）通道代表了哺乳动物中钙库操纵的钙进入的典型实例。ORAI-STIM信号传导发生在内质网（ER）和质膜之间紧密并置形成的膜接触位点。ORAI 1是一种四通道跨膜蛋白，在质膜中形成高度钙选择性的离子通道。STIM 1是一种ER驻留的单次跨膜蛋白，作为ER腔内的钙传感器和ORAI 1钙通道的有效激活剂。奥赖和STIM之间复杂的相互作用控制钙进入细胞以调节无数的生理过程。本文重点介绍了CRAC通道的结构-功能关系，重点介绍了调控STIM 1构象转换的关键结构元件以及STIM 1和ORAI 1之间的动态耦合。此外，我们还讨论了STIM-ORAI信号在各种组织和器官中的生理作用，以及人类ORAI 1和STIM 1功能丧失或获得突变引起的主要病理状况。(C)2018美国生理学会
The calcium release-activated calcium (CRAC) channel, composed of ORAI and stromal interaction molecules (STIM), represents a prototypical example of store-operated calcium entry in mammals. The ORAI-STIM signaling occurs at membrane contact sites formed by close appositions between the endoplasmic reticulum (ER) and the plasma membrane. ORAI1 is a four-pass transmembrane protein that forms a highly calcium-selective ion channel in the plasma membrane. STIM1 is an ER-resident, a single-pass transmembrane protein that serves as a calcium sensor within the ER lumen and a potent activator of ORAI1 calcium channels. The intricate interplay between ORAI and STIM controls calcium entry into cells to regulate a myriad of physiological processes. We highlight herein the current knowledge on the structure-function relationship of CRAC channel, with a focus on key structural elements that mediate STIM1 conformational switch and the dynamic coupling between STIM1 and ORAI1. Furthermore, we discuss the physiological roles of STIM-ORAI signaling in various tissues and organs, as well as major pathological conditions arising from loss-or gain-of-function mutations in human ORAI1 and STIM1. (C) 2018 American Physiological Society.