CRAC通道的生理功能。

IF 15.7 1区 医学 Q1 PHYSIOLOGY
Annual review of physiology Pub Date : 2022-02-10 Epub Date: 2021-10-12 DOI:10.1146/annurev-physiol-052521-013426
Scott M Emrich, Ryan E Yoast, Mohamed Trebak
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引用次数: 37

摘要

储存操作的Ca2+进入(SOCE)是一种普遍存在的Ca2+信号通路,在真核生物中进化保守。当内质网(ER)Ca2+储存通过激活肌醇1,4,5-三磷酸受体而被清空时,SOCE在生理上被触发。SOCE由Ca2+释放激活的Ca2+(CRAC)通道介导,该通道具有高度的Ca2+选择性。在储存耗尽时,ER Ca2+感应STIM蛋白聚集并获得跨越ER质膜连接空间的延伸构象,以结合和激活Orai,即六聚体CRAC通道的成孔蛋白。近年来,对STIM和Orai组织特异性敲除小鼠以及人类功能获得和丧失突变的研究揭示了SOCE在各种组织中的生理功能。在这里,我们描述了关于天然CRAC通道的组成及其在免疫、肌肉、分泌和神经元系统中的生理功能的最新发现,以从转基因小鼠和由CRAC通道活性改变引起的人类疾病中吸取教训。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Physiological Functions of CRAC Channels.

Store-operated Ca2+ entry (SOCE) is a ubiquitous Ca2+ signaling pathway that is evolutionarily conserved across eukaryotes. SOCE is triggered physiologically when the endoplasmic reticulum (ER) Ca2+ stores are emptied through activation of inositol 1,4,5-trisphosphate receptors. SOCE is mediated by the Ca2+ release-activated Ca2+ (CRAC) channels, which are highly Ca2+ selective. Upon store depletion, the ER Ca2+-sensing STIM proteins aggregate and gain extended conformations spanning the ER-plasma membrane junctional space to bind and activate Orai, the pore-forming proteins of hexameric CRAC channels. In recent years, studies on STIM and Orai tissue-specific knockout mice and gain- and loss-of-function mutations in humans have shed light on the physiological functions of SOCE in various tissues. Here, we describe recent findings on the composition of native CRAC channels and their physiological functions in immune, muscle, secretory, and neuronal systems to draw lessons from transgenic mice and human diseases caused by altered CRAC channel activity.

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来源期刊
Annual review of physiology
Annual review of physiology 医学-生理学
CiteScore
35.60
自引率
0.00%
发文量
41
期刊介绍: Since 1939, the Annual Review of Physiology has been highlighting significant developments in animal physiology. The journal covers diverse areas, including cardiovascular physiology, cell physiology, ecological, evolutionary, and comparative physiology, endocrinology, gastrointestinal physiology, neurophysiology, renal and electrolyte physiology, respiratory physiology, and special topics.
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