Plasma membrane localization of TRPC channels: role of caveolar lipid rafts.
Plasma membrane localization of TRPC channels: role of caveolar lipid rafts.
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DOI：
10.1002/0470862580.ch5
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发表时间：
2004
影响因子：
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通讯作者：
I. Ambudkar;So-ching Brazer;Xibao Liu;T. Lockwich;Brij B. Singh
中科院分区：
文献类型：
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作者：
I. Ambudkar;So-ching Brazer;Xibao Liu;T. Lockwich;Brij B. Singh
GPCR 介导的 Ca2+ 信号级联激活会刺激 Ca2+ 流入非兴奋性细胞。依赖于储存的通道和独立的通道都可能有助于 Ca2+ 的流入。然而，通道的身份和激活它们的确切机制仍然难以捉摸。 TRPC 蛋白家族已被提议作为这些通道的分子成分。我们实验室和其他实验室的研究表明，哺乳动物 TRPC 蛋白组装成多蛋白复合物，其中包括各种关键的 Ca2+ 信号蛋白。然而，对于质膜中 TRPC 通道复合物组装所涉及的机制知之甚少。我们报道了 TRPC1 和 TRPC3 信号复合物与质膜中的小凹脂筏结构域 (LRD) 相关。最近我们研究了 Caveolin-1 在 TRPC 通道和钙库操纵的 Ca2+ 内流 (SOCE) 调节中的作用。根据我们的研究，我们认为（1）caveolin 1 在 TRPC 通道质膜小凹 LRD 的定位中具有潜在的关键作用，（2）小凹的分子结构可以促进 TRPC 通道和参与 SOCE 激活和/或失活的相关蛋白之间的分子内相互作用。
GPCR-mediated activation of the Ca2+ signalling cascade leads to stimulation of Ca2+ influx into non-excitable cells. Both store-dependent and independent channels likely contribute towards this Ca2+ influx. However, the identity of the channels and exact mechanism by which they are activated remains elusive. The TRPC family of proteins has been proposed as molecular components of these channels. Studies from our laboratory and others have shown that mammalian TRPC proteins are assembled in a multiprotein complex that includes various key Ca2+ signalling proteins. However, relatively little is known regarding the mechanisms involved in the assembly of the TRPC channel complex in the plasma membrane. We have reported that TRPC1 and TRPC3 signalling complexes are associated with caveolar lipid raft domains (LRDs) in the plasma membrane. Recently we have examined the role of caveolin-1 in the regulation of TRPC channels and store-operated Ca2+ entry (SOCE). Based on our studies, we suggest that (1) caveolin 1 has a potentially critical role in the localization of TRPC channels plasma membrane caveolar LRDs, and (2) the molecular architecture of caveolae can facilitate intramolecular interactions between TRPC channels and associated proteins that are involved in activation and/or inactivation of SOCE.