Contribution of TRPC1 and Orai1 to Ca(2+) entry activated by store depletion.
Contribution of TRPC1 and Orai1 to Ca(2+) entry activated by store depletion.
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DOI：
10.1007/978-94-007-0265-3_24
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发表时间：
2011
影响因子：
--
通讯作者：
Ambudkar, Indu S.
中科院分区：
文献类型：
--
作者：
Cheng, Kwong Tai;Ong, Hwei Ling;Liu, Xibao;Ambudkar, Indu S.
储存操纵的 Ca2+ 进入 (SOCE) 因 ER Ca2+ 传感器蛋白 STIM1 耗尽 ER-Ca2+ 储存而被激活，STIM1 寡聚化并移动到 ER/PM 连接域，在此处与 SOCE 涉及的通道相互作用并激活通道。已经描述了两种类型的渠道活动。 ICRAC，通过 Ca2+ 释放激活的 Ca2+ (CRAC) 通道，显示出高 Ca2+ 选择性，并负责 T 淋巴细胞、肥大细胞、血小板以及某些类型的平滑肌和内皮细胞的 SOCE 和细胞功能。 Orai1 已被确定为 CRAC 通道的成孔成分，并且 Orai1 和 STIM1 的相互作用足以生成 CRAC 通道。储存耗尽还会导致相对非选择性的阳离子电流（称为 ISOC）的激活，这有助于其他几种细胞类型的 SOCE。 TRPC 通道，包括 TRPC1、TRPC3、TRPC4，已被提议作为 Ca2+ 流入的可能候选通道。 TRPC1 是这方面最具特征的通道，据报道在许多细胞类型中有助于内源性 SOCE。在用激动剂或毒胡萝卜素刺激的细胞中，TRPC1 介导的 Ca2+ 进入和阳离子电流受到低 [Gd3+] 和 10–20 μM 2APB（阻断 SOCE 的条件）的抑制。重要的是，STIM1 还通过 STIM1 (684KK685) 和 TRPC1 (639DD640) 之间的静电相互作用与 TRPC1 关联并门控 TRPC1。此外，存储耗尽会诱导 TRPC1/STIM1/Orai1 复合物的动态募集，而 Orai1 的敲除会完全消除 TRPC1 功能。尽管有这些发现，关于 TRPC1 存储耗尽的激活以及 Orai1 和 STIM1 在 SOC 通道功能中的作用仍然存在很多争论。本章总结了有关 Orai1 和 TRPC1 对 SOCE 贡献的最新研究和概念。将讨论有关 Orai1 和 TRPC1 之间功能相互作用的主要未解决问题，以及通过存储耗尽调节 TRPC 通道的可能机制。
Store-operated Ca2+ entry (SOCE) is activated in response to depletion of the ER-Ca2+ stores by the ER Ca2+ sensor protein, STIM1 which oligomerizes and moves to ER/PM junctional domains where it interacts with and activates channels involved in SOCE. Two types of channel activities have been described. ICRAC, via Ca2+ release-activated Ca2+ (CRAC) channel, which displays high Ca2+ selectivity and accounts for the SOCE and cell function in T lymphocytes, mast cells, platelets, and some types of smooth muscle and endothelial cells. Orai1 has been established as the pore-forming component of CRAC channels and that interaction of Orai1 and STIM1 is sufficient for generation of the CRAC channel. Store depletion also leads to activation of relatively non-selective cation currents (referred to as ISOC) that contribute to SOCE in several other cell types. TRPC channels, including TRPC1, TRPC3, TRPC4, have been proposed as possible candidate channels for this Ca2+ influx. TRPC1 is the best characterized channel in this regard and reported to contribute to endogenous SOCE in many cells types. TRPC1-mediated Ca2+ entry and cation current in cells stimulated with agonist or thapsigargin were inhibited by low [Gd3+] and 10–20 μM 2APB (conditions that block SOCE). Importantly, STIM1 also associates with and gates TRPC1 via electrostatic interaction between STIM1 (684KK685) and TRPC1 (639DD640). Further, store depletion induces dynamic recruitment of a TRPC1/STIM1/Orai1 complex and knockdown of Orai1 completely abrogates TRPC1 function. Despite these findings, there has been much debate regarding the activation of TRPC1 by store depletion as well as the role of Orai1 and STIM1 in SOC channel function. This chapter summarizes recent studies and concepts regarding the contributions of Orai1 and TRPC1 to SOCE. Major unresolved questions regarding functional interaction between Orai1 and TRPC1 as well as possible mechanisms involved in the regulation of TRPC channels by store depletion will be discussed.
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影响因子：
4
作者：
Alicia, Sampieri;Angelica, Zepeda;Vaca, Luis
通讯作者：
Vaca, Luis
影响因子：
2.4
作者：
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绘制 Ca2 释放激活的 Ca2 通道激活中 STIM1 和 Orai1 的相互作用域
影响因子：
4.8
作者：
Li, Zhengzheng;Lu, Jingze;Xu, Tao
通讯作者：
Xu, Tao