Store-operated Orai channels: structure and function.
Store-operated Orai channels: structure and function.
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DOI：
10.1016/b978-0-12-407870-3.00001-9
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发表时间：
2013
影响因子：
--
通讯作者：
Prakriya, Murali
中科院分区：
文献类型：
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作者：
Prakriya, Murali
在许多动物细胞中，钙库操纵的 Ca2+ 释放激活的 Ca2+ (CRAC) 通道是 Ca2+ 进入的重要途径。 CRAC 通道控制许多基本细胞功能，包括基因表达、运动和细胞增殖，参与包括严重联合免疫缺陷综合征在内的多种疾病过程的病因学，并已成为药物开发的主要目标。尽管几十年来人们对CRAC通道运作的分子机制知之甚少，但Orai1作为原型CRAC通道蛋白和STIM1作为内质网(ER) Ca2+传感器的发现使我们对CRAC通道机制和功能的理解取得了快速进展。现在已知，ER Ca2+储备耗尽后 CRAC 通道的激活是由几个事件控制的，其中包括 STIM1 和 Orai1 重新分布和积累到外周细胞位点的重叠斑点中，从而导致两种蛋白质之间直接的蛋白质-蛋白质相互作用。在本章中，我回顾了调节 CRAC 通道门控和离子传导机制的 STIM 和 Orai 蛋白的分子特征。
In many animal cells, store-operated Ca2+ release-activated Ca2+ (CRAC) channels function as an essential route for Ca2+ entry. CRAC channels control many fundamental cellular functions including gene expression, motility, and cell proliferation, are involved in the etiology of several disease processes including a severe combined immunodeficiency syndrome, and have emerged as major targets for drug development. Although little was known of the molecular mechanisms of CRAC channel operation for several decades, the discovery of Orai1 as a prototypic CRAC channel protein and STIM1 as the endoplasmic reticulum (ER) Ca2+ sensor has led to rapid progress in our understanding of the mechanisms and functions of CRAC channels. It is now known that activation of CRAC channels following ER Ca2+ store depletion is governed by several events, which include the redistributions and accumulations of STIM1 and Orai1 into overlapping puncta at peripheral cellular sites, resulting in direct protein–protein interactions between the two proteins. In this chapter, I review the molecular features of the STIM and Orai proteins that regulate the gating and ion conduction mechanisms of CRAC channels.