Lipid rafts/caveolae as microdomains of calcium signaling.
Lipid rafts/caveolae as microdomains of calcium signaling.
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DOI：
10.1016/j.ceca.2009.02.009
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发表时间：
2009-06
期刊：
影响因子：
4
通讯作者：
Singh BB
中科院分区：
文献类型：
--
作者：
Pani B;Singh BB
Ca 2+是可兴奋和非可兴奋细胞中的主要信号分子，在其中它发挥从细胞生长到分化到细胞死亡的关键功能。这些细胞的生理功能响应于胞质Ca 2+的变化而受到严格调节，胞质Ca 2+的变化是通过激活几个质膜（PM）Ca 2+通道以及从内部储存释放Ca 2+来实现的。一种这样的通道被称为钙库操纵的Ca 2+通道，其通过内质网（ER）Ca 2+的释放激活，内质网（ER）Ca 2+的释放启动钙库操纵的Ca 2+进入（SOCE）。该领域的最新进展表明，TRPC和奥赖通道的一些成员具有SOCE通道的功能。然而，调节通道活性的分子机制以及这些通道组装和调节的确切性质仍然难以捉摸。几个实验室的研究表明，参与Ca 2+信号传导的关键蛋白定位于离散的PM脂筏/小窝微区。脂筏是富含胆固醇和鞘脂的微结构域，作为独特的信号转导平台。此外，脂筏本质上是动态的，其倾向于支架某些信号分子而排除其他分子。通过这种空间分离，脂筏不仅为分子内串扰提供了有利的环境，而且有助于加快信号传递。重要的是，Ca 2+信号被证明是从这些脂筏微结构域开始的。Ca 2+通道及其调节因子在此类微结构域中的聚集可以对Ca 2+介导的细胞功能提供精致的时空调节。因此，在这篇综述中，我们讨论PM脂筏和小窝作为Ca 2+信号微域，并强调其在组织和调节SOCE通道的重要性。
Ca2+ is a major signaling molecule in both excitable and non-excitable cells, where it serves critical functions ranging from cell growth to differentiation to cell death. The physiological functions of these cells are tightly regulated in response to changes in cytosolic Ca2+ that is achieved by the activation of several plasma membrane (PM) Ca2+ channels as well as release of Ca2+ from the internal stores. One such channel is referred to as store-operated Ca2+ channel that is activated by the release of endoplasmic reticulum (ER) Ca2+ which initiates store operated Ca2+ entry (SOCE). Recent advances in the field suggest that some members of TRPCs and Orai channels function as SOCE channels. However, the molecular mechanisms that regulate channel activity and the exact nature of where these channels are assembled and regulated remain elusive. Research from several laboratories has demonstrated that key proteins involved in Ca2+ signaling are localized in discrete PM lipid rafts/caveolar microdomains. Lipid rafts are cholesterol and sphingolipid enriched microdomains that function as unique signal transduction platforms. In addition lipid rafts are dynamic in nature which tends to scaffold certain signaling molecules while excluding others. By such spatial segregation, lipid rafts not only provide a favorable environment for intra-molecular cross talk but also aid to expedite the signal relay. Importantly, Ca2+ signaling is shown to initiate from these lipid raft microdomains. Clustering of Ca2+ channels and their regulators in such microdomains can provide an exquisite spatiotemporal regulation of Ca2+ mediated cellular function. Thus in this review we discuss PM lipid rafts and caveolae as Ca2+ signaling microdomains and highlight their importance in organizing and regulating SOCE channels.
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