Ong Hwei Ling, Ambudkar Indu S
Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.
Cell Calcium. 2015 Oct;58(4):376-86. doi: 10.1016/j.ceca.2015.03.008. Epub 2015 Apr 10.
Store-operated calcium entry (SOCE) is activated within the endoplasmic reticulum (ER)-plasma membrane (PM) junctions in the plasma membrane and involves assembly of the channels, Orai1 and TRPC1, with the regulatory protein, STIM1, in response to depletion of Ca(2+) in the ER. The dynamic assembly of the channel complexes as well as regulation of channel activity and cell function is dependent on critical components that are either already localized in and/or recruited to the junctions following cell stimulation. These include proteins and lipids in the plasma membrane, ER, and cytosol. Together, these coordinated interactions lead to assembly and activation of Orai1/STIM1 and TRPC1/STIM1 channels. Recent studies demonstrate that Ca(2+) signals generated by Orai1 are detected locally within the ER-PM junctions by various signaling proteins that trigger and regulate other Ca(2+)-dependent functions. One such function is the plasma membrane recruitment of TRPC1 channels where it is activated by STIM1. Activation of TRPC1 within the ER-PM junctions leads to generation of distinct [Ca(2+)]i signals and regulation of cellular functions different from those regulated by Orai1. Thus, it has been suggested that Orai1 and TRPC1 channels are compartmentalized in distinct microdomains. Such compartmentalization involves organization of plasma membrane lipids as well as structural and scaffolding proteins, the nature of which is still poorly understood. Importantly, there appears to be dynamic reorganization of the microdomains within existing ER-PM junctions that allow segregated proteins to interact. Together, these highly specific and coordinated remodeling of protein complexes and membrane domains results in generation of spatially- and temporally-controlled Ca(2+) signals that are critical for numerous downstream cellular functions.
钙库操纵性钙内流（SOCE）在内质网（ER）-质膜（PM）连接处的质膜内被激活，涉及通道蛋白Orai1和TRPC1与调节蛋白STIM1的组装，以响应内质网中Ca(2+)的耗竭。通道复合物的动态组装以及通道活性和细胞功能的调节取决于细胞刺激后已定位在连接处和/或募集到连接处的关键成分。这些成分包括质膜、内质网和胞质溶胶中的蛋白质和脂质。这些协调的相互作用共同导致Orai1/STIM1和TRPC1/STIM1通道的组装和激活。最近的研究表明，Orai1产生的Ca(2+)信号在ER-PM连接处被各种信号蛋白局部检测到，这些信号蛋白触发并调节其他Ca(2+)依赖性功能。其中一种功能是TRPC1通道在质膜上的募集，在那里它被STIM1激活。ER-PM连接处TRPC1的激活导致产生与Orai1调节的不同的独特的[Ca(2+)]i信号和细胞功能调节。因此，有人提出Orai1和TRPC1通道被分隔在不同的微结构域中。这种分隔涉及质膜脂质以及结构和支架蛋白的组织，其性质仍知之甚少。重要的是，现有ER-PM连接处的微结构域似乎存在动态重组，使分离的蛋白质能够相互作用。这些蛋白质复合物和膜结构域的高度特异性和协调性重塑共同导致产生对众多下游细胞功能至关重要的时空控制的Ca(2+)信号。
