Some assembly required:: Constructing the elementary units of store-operated Ca2+ entry
Some assembly required:: Constructing the elementary units of store-operated Ca2+ entry
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DOI：
10.1016/j.ceca.2007.03.003
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发表时间：
2007-08-01
期刊：
影响因子：
4
通讯作者：
Lewis, Richard S.
中科院分区：
文献类型：
--
作者：
Wu, Minnie M.;Luik, Riina M.;Lewis, Richard S.
Ca(2+)库耗竭是如何引起可兴奋和不可兴奋细胞质膜上库操作的钙通道(SOCs)开放的，这是一个长期未解的谜。间接证据支持ER和SOC之间的局部相互作用，以及通过可扩散的激活剂调节的远程相互作用。最近分子鉴定的内质网钙传感器(STIM1)和CRAC通道的一个亚单位(Orai 1)，一个典型的SOC，现在已经有可能直接可视化的事件序列联系起来的存储枯竭和CRAC通道开放。在存储耗尽后，STIM1从整个内质网的各个位置移动到位于质膜10-25 nm范围内的内质网亚区。同时，Orai I聚集在质膜上STIM1正对面的离散位置，导致局部CRAC通道激活。这些新的研究定义了存储操作的钙离子进入的基本单位，并揭示了一种前所未有的通道激活机制，在这种机制中，刺激将通道及其激活器/传感器聚集在一起，以跨越相对的膜间隔进行相互作用。我们讨论了这种编排机制对钙动力学的影响，钙信号的特异性，以及专用于控制CRAC通道的特殊内质网子集的存在。(C)2007爱思唯尔有限公司。保留所有权利。
The means by which Ca(2+) store depletion evokes the opening of store-operated Ca(2+) channels (SOCs) in the plasma membrane of excitable and non-excitable cells has been a longstanding mystery. Indirect evidence has supported local interactions between the ER and SOCs as well as long-range interactions mediated through a diffusible activator. The recent molecular identification of the ER Ca2+ sensor (STIM1) and a subunit of the CRAC channel (Orai 1), a prototypic SOC, has now made it possible to visualize directly the sequence of events that links store depletion to CRAC channel opening. Following store depletion, STIM1 moves from locations throughout the ER to accumulate in ER subregions positioned within 10-25 nm of the plasma membrane. Simultaneously, Orai I gathers at discrete sites in the plasma membrane directly opposite STIM1, resulting in local CRAC channel activation. These new studies define the elementary units of store-operated Ca2+ entry, and reveal an unprecedented mechanism for channel activation in which the stimulus brings a channel and its activator/sensor together for interaction across apposed membrane compartments. We discuss the implications of this choreographic mechanism with regard to Ca2+ dynamics, specificity of Ca2+ signaling, and the existence of a specialized ER subset dedicated to the control of the CRAC channel. (C) 2007 Elsevier Ltd. All rights reserved.