TRPC channels as STIM1 - regulated store-operated channels
TRPC channels as STIM1 - regulated store-operated channels
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DOI：
10.1016/j.ceca.2007.03.004
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发表时间：
2007-08-01
期刊：
影响因子：
4
通讯作者：
Muallem, Shmuel
中科院分区：
文献类型：
--
作者：
Worley, Paul F.;Zeng, Weizhong;Muallem, Shmuel
受体激活的 Ca2+ 流入主要由钙池操纵通道 (SOC) 介导。 TRPC 通道介导受体激活的 Ca2+ 流入的很大一部分。然而，TRPC 通道是否具有 SOC 功能仍存在争议。随着 STIM I 在 Ca2+ 流入通道调节中的作用的发现，我们对 TRPC 通道的调节及其作为 SOC 功能的理解正在被重塑。 STIM1 是一种内质网驻留的 Ca2+ 结合蛋白，可调节 SOC，这一发现允许对 SOC 进行扩展的分子定义。 SOC 可以被认为是受 STIM I 调节的通道，并且需要 STIM I 聚集来响应 ER Ca2+ 储备的耗尽及其向质膜的易位。 TRPC1 和其他 TRPC 通道满足这些标准。 STIM1 与 TRPC1、TRPC2、TRPC4 和 TRPC5 结合，但不与 TRPC3、TRPC6 和 TRPC7 结合，并且 STIM1 调节 TRPC1 通道活性。结构功能分析表明，STIM1的C端包含STIM1的结合和门控功能。STIM1的ERM结构域与TRPC通道结合，富含赖氨酸的区域参与SOC和TRPC1的门控。通过 siRNA 敲低 STIM1 并防止其易位至质膜，可抑制天然 SOC 和 TRPC 1 的活性。这些发现支持 TRPC I 是 SOC 的结论。对其他 TRPC 通道的类似研究证明了它们受到 STIM1 的调节，并表明除 TRPC7 之外的所有 TRPC 通道都充当 SOC。 (C) 2007 Elsevier Ltd. 保留所有权利。
Receptor- activated Ca2+ influx is mediated largely by store-operated channels (SOCs). TRPC channels mediate a significant portion of the receptor- activated Ca2+, influx. However, whether any of the TRPC channels function as a SOC remains controversial. Our understanding of the regulation of TRPC channels and their function as SOCs is being reshaped with the discovery of the role of STIM I in the regulation of Ca2+, influx channels. The findings that STIM1 is an ER resident Ca2+ binding protein that regulates SOCs allow an expanded and molecular definition of SOCs. SOCs can be considered as channels that are regulated by STIM I and require the clustering of STIM I in response to depletion of the ER Ca2+ stores and its translocation towards the plasma membrane. TRPC1 and other TRPC channels fulfill these criteria. STIM1 binds to TRPC1, TRPC2, TRPC4 and TRPC5 but not to TRPC3, TRPC6 and TRPC7, and STIM1 regulates TRPC1 channel activity. Structure-function analysis reveals that the C-terminus of STIM1 contains the binding and gating function of STIM1 The ERM domain of STIM1 binds to TRPC channels and a lysine-rich region participates in the gating of SOCs and TRPC1. Knock-down of STIM1 by siRNA and prevention of its translocation to the plasma membrane inhibit the activity of native SOCs and TRPC 1. These findings support the conclusion that TRPC I is a SOC. Similar studies with other TRPC channels demonstrate their regulation by STIM1 and indicate that all TRPC channels, except TRPC7, function as SOCs. (C) 2007 Elsevier Ltd. All rights reserved.