STIM2 is a feedback regulator that stabilizes basal cytosolic and endoplasmic reticulum Ca2+ levels
STIM2 is a feedback regulator that stabilizes basal cytosolic and endoplasmic reticulum Ca2+ levels
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DOI：
10.1016/j.cell.2007.11.039
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发表时间：
2007-12-28
期刊：
影响因子：
64.5
通讯作者：
Meyer, Tobias
中科院分区：
文献类型：
--
作者：
Brandman, Onn;Liou, Jen;Meyer, Tobias
基础Ca2+水平的偏差干扰受体介导的Ca2+信号传导以及内质网（ER）和线粒体功能。虽然有缺陷的基础Ca2+调节与各种疾病有关，但对控制基础Ca2+的调节机制知之甚少。在这里，我们进行了一个人信号蛋白质组的siRNA筛选，以确定基础Ca2+浓度的调节剂，并发现STIM2作为最强的正调节剂。与最近发现的响应于受体介导的ER Ca2+储存耗尽而触发Ca2+内流的信号转导物STIM1相反，STIM2在ER Ca2+的较小降低时激活Ca2+内流。与STIM1一样，STIM2通过激活质膜Ca 2+通道Orai1引起Ca 2+内流。我们的研究将STIM2置于反馈模块的中心，该反馈模块将基础细胞质和ER Ca2+浓度保持在严格的限制范围内。
Deviations in basal Ca2+ levels interfere with receptor-mediated Ca2+ signaling as well as endoplasmic reticulum ( ER) and mitochondrial function. While defective basal Ca2+ regulation has been linked to various diseases, the regulatory mechanism that controls basal Ca2+ is poorly understood. Here we performed an siRNA screen of the human signaling proteome to identify regulators of basal Ca2+ concentration and found STIM2 as the strongest positive regulator. In contrast to STIM1, a recently discovered signal transducer that triggers Ca2+ influx in response to receptor-mediated depletion of ER Ca2+ stores, STIM2 activated Ca2+ influx upon smaller decreases in ER Ca2+. STIM2, like STIM1, caused Ca2+ influx via activation of the plasma membrane Ca2+ channel Orai1. Our study places STIM2 at the center of a feedback module that keeps basal cytosolic and ER Ca2+ concentrations within tight limits.