STIM1 signalling controls store-operated calcium entry required for development and contractile function in skeletal muscle
STIM1 signalling controls store-operated calcium entry required for development and contractile function in skeletal muscle
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DOI：
10.1038/ncb1731
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发表时间：
2008-06-01
影响因子：
21.3
通讯作者：
Rosenberg, Paul
中科院分区：
文献类型：
--
作者：
Stiber, Jonathan;Hawkins, April;Rosenberg, Paul
现在已经确定基质相互作用分子1（stromal interaction molecule 1，STIM 1）是激活非兴奋细胞表面的钙库操纵的钙进入（store-operated calcium entry，SOC）通道所需的内质网钙传感器。然而，很少有人知道STIM 1在兴奋性细胞，如横纹肌，其中钙调节分子的补充是相当不同的非兴奋性细胞。在这里，我们表明，STIM 1在肌管和成人骨骼肌中表达。缺乏功能性STIM 1的肌管不能快速显示SOC和疲劳。此外，缺乏功能性STIM 1的小鼠在围产期死于骨骼肌病。此外，STIM 1单倍不足仅在需要快速重新填充储存的条件下赋予收缩缺陷。这些发现提供了对STIM 1在骨骼肌中的作用的深入了解，并表明STIM 1在可兴奋和不可兴奋细胞中作为ER/SR钙传感器具有普遍作用。
It is now well established that stromal interaction molecule 1 (STIM1) is the calcium sensor of endoplasmic reticulum stores required to activate store-operated calcium entry (SOC) channels at the surface of non-excitable cells. However, little is known about STIM1 in excitable cells, such as striated muscle, where the complement of calcium regulatory molecules is rather disparate from that of non-excitable cells. Here, we show that STIM1 is expressed in both myotubes and adult skeletal muscle. Myotubes lacking functional STIM1 fail to show SOC and fatigue rapidly. Moreover, mice lacking functional STIM1 die perinatally from a skeletal myopathy. In addition, STIM1 haploinsufficiency confers a contractile defect only under conditions where rapid refilling of stores would be needed. These findings provide insight into the role of STIM1 in skeletal muscle and suggest that STIM1 has a universal role as an ER/SR calcium sensor in both excitable and non-excitable cells.