STIM1 converts TRPC1 from a receptor-operated to a store-operated channel: Moving TRPC1 in and out of lipid rafts
STIM1 converts TRPC1 from a receptor-operated to a store-operated channel: Moving TRPC1 in and out of lipid rafts
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DOI：
10.1016/j.ceca.2008.03.001
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发表时间：
2008-11-01
期刊：
影响因子：
4
通讯作者：
Vaca, Luis
中科院分区：
文献类型：
--
作者：
Alicia, Sampieri;Angelica, Zepeda;Vaca, Luis
虽然TRPC通道家族成员作为受体操纵性通道（ROC）的作用已得到充分确立，并得到众多研究的支持，但在过去几年中，该通道家族作为储存操纵性通道（SOC）的作用一直是激烈争论的焦点。在本研究中，我们探讨了STIM1对人TRPC1通道的调节作用。我们发现STIM1与TRPC1的结合有利于TRPC1插入脂筏，在脂筏中TRPC1作为SOC发挥作用。在没有STIM1的情况下，TRPC1与TRPC通道家族的其他成员结合形成ROCs。一种新的全内反射荧光显微镜 - 荧光共振能量转移（TIRFM - FRET）方法阐明了STIM1和TRPC1之间的动态结合对于SOC的激活以及STIM1 - TRPC1复合物在脂筏定位的相关性。这项研究为TRPC1的双重活性（形成ROC或SOC）以及决定TRPC1功能命运所需的伙伴提供了新的证据。它还强调了质膜微区和内质网 - 质膜连接在调节TRPC1通道功能及其与STIM1的结合方面的作用。0 2008爱思唯尔有限公司。保留所有权利。
White the role of members from the TRPC family of channels as receptor-operated channels (ROC) is well established and supported by numerous studies, the role of this family of channels as store-operated channels (SOC) has been the focus of a heated controversy over the last few years. In the present study, we have explored the modulation of STIM1 on human TRPC1 channel. We show that the association of STIM1 to TRPC1 favors the insertion of TRPC1 into lipid rafts, where TRPC1 functions as a SOC. In the absence of STIM1, TRPC1 associates to other members from the TRPC family of channels to form ROCs. A novel TIRFM-FRET method illustrates the relevance of the dynamic association between STIM1 and TRPC1 for the activation of SOC and the lipid raft localization of the STIM1-TRPC1 complex. This study provides new evidence about the dual activity of TRPC1 (forming ROC or SOC) and the partners needed to determine TRPC1 functional fate. It highlights also the role of plasma membrane microdomains and ER-PM junctions in modulating TRPC1 channel function and its association to STIM1. 0 2008 Elsevier Ltd. All rights reserved.