Coupling of STIM1 to store-operated Ca2+ entry through its constitutive and inducible movement in the endoplasmic reticulum
Coupling of STIM1 to store-operated Ca2+ entry through its constitutive and inducible movement in the endoplasmic reticulum
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DOI：
10.1073/pnas.0608358103
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发表时间：
2006-11-07
影响因子：
11.1
通讯作者：
Kurosaki, Tomohiro
中科院分区：
文献类型：
--
作者：
Baba, Yoshihiro;Hayashit, Kenji;Kurosaki, Tomohiro
细胞内钙(Ca~(2+))库的耗竭诱导钙库操作的钙(SOC)跨质膜(PM)进入。STIM1是内质网(ER)中一种可能的钙感受器，最近被证明是SOC通道激活所必需的。在这里，我们显示STIM1在静息活细胞的内质网及其亚室上以管状室的形式动态移动，而当钙存储耗尽时，STIM1迅速重新分布到离散的点状结构中，这些点状结构位于内质网下面，但不插入PMSTIM1的正常结构性运动是通过STIM1细胞质区域的盘绕线圈和富含Ser/Thr的C-末端结构域介导的，而随后可诱导的点状结构域的形成进一步需要无菌的a基序结构域突出到内质网腔中。这三个结构域(卷曲卷曲、富含丝氨酸/苏氨酸和无菌a基序)都是激活SOC通道所必需的。因此，我们基于结构-功能实验的发现表明，STIM1在内质网及其亚室中的结构性动态运动对于随后STIM1在PM下的Puneta中的依赖耗竭的重新分布和SOC通道的激活是必需的。
Depletion of intracellular calcium (Ca2+) stores induces store-operated Ca2+ (SOC) entry across the plasma membrane (PM). STIM1, a putative Ca2+ sensor in the endoplasmic reticulum (ER), has been recently shown to be necessary for SOC channel activation. Here we show that STIM1 dynamically moves in tubulovesicular shape on the ER and its subcompartment in resting living cells, whereas, upon Ca2+ store depletion, it is rapidly redistributed into discrete puncta that are located underneath, but not inserted into the PM. Normal constitutive movement of STIM1 is mediated through the coiled-coil and Ser/Thr-rich C-terminal domains in the cytoplasmic region of STIM1, whereas subsequent inducible puncta formation further requires the sterile a motif domain protruding into the ER lumen. Each of these three domains (coiled-coil, Ser/Thr-rich, and sterile a motif) was essential for activating SOC channels. Hence, our findings based on structure-function experiments suggest that constitutive dynamic movement of STIM1 in the ER and its subcompartment is obligatory for subsequent depletion-dependent redistribution of STIM1 into puneta underneath the PM and activation of SOC channels.