The closing and opening of TRPC channels by Homer1 and STIM1.
The closing and opening of TRPC channels by Homer1 and STIM1.
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DOI：
10.1111/j.1748-1716.2011.02319.x
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发表时间：
2012-02
期刊：
影响因子：
--
通讯作者：
Muallem S
中科院分区：
文献类型：
--
作者：
Yuan JP;Lee KP;Hong JH;Muallem S
Ca~(2+)内流是受体诱导的Ca~(2+)信号的中心成分。一种普遍存在的钙离子内流形式来自内质网钙库耗尽时激活的钙通道，因此被称为库操作的钙内流通道(SOCs)。SOC的一种形式是瞬时受体电位典范(TRPC)通道。钙离子信号转导领域的一个主要问题是调节这些通道的开放和关闭的分子机制。所有的TRPC通道都有一个荷马结合配体和两个保守的负电荷，它们与基质相互作用分子1(STIM1)的两个末端赖氨酸相互作用。Hmer和STIM1位点之间只有四个氨基酸残基。根据已有的结果，我们提出了一种分子机制，即荷马将TRPC通道与IP3受体(IP3Rs)偶联，以保持这些通道处于关闭状态。TRPC-Hmer-IP3Rs复合体的解离允许STIM1访问TRPC通道，负电荷门控打开这些通道。
Ca2+ influx is a central component of the receptor-evoked Ca2+ signal. A ubiquitous form of Ca2+ influx comes from Ca2+ channels that are activated in response to depletion of the endoplasmic reticulum Ca2+ stores and are thus named the store-operated Ca2+-influx channels (SOCs). One form of SOCs is the Transient Receptor Potential Canonical (TRPC) channels. A major question in the field of Ca2+ signaling is the molecular mechanism that regulates the opening and closing of these channels. All TRPC channels have a Homer binding ligand and two conserved negative charges that interact with two terminal lysines of the Stromal Interacting Molecule 1 (STIM1). The Homer and STIM1 sites are separated by only four amino acid residues. Based on available results, we propose a molecular mechanism by which Homer couples TRPC channels to IP3 receptors (IP3Rs) to keep these channels in the closed state. Dissociation of the TRPCs-Homer-IP3Rs complex allows STIM1 access to the TRPC channels negative charges to gate open these channels.
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