ER membrane protein complex 1 interacts with STIM1 and regulates store-operated Ca2+ entry
ER membrane protein complex 1 interacts with STIM1 and regulates store-operated Ca2+ entry
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DOI：
10.1093/jb/mvab063
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发表时间：
2021-05-20
影响因子：
2.7
通讯作者：
Baba, Yoshihiro
中科院分区：
文献类型：
--
作者：
Kawata, Kazuhiko;Baba, Akemi;Baba, Yoshihiro
储存操作钙进入（SOCE）是内质网（ER） Ca2+储存的排空导致Ca2+通过质膜（PM）流入的过程。它是不可兴奋细胞中Ca2+内流的主要途径，具有广泛的生理功能。当储存耗尽时，基质相互作用分子1 (STIM1)，一个内质网钙传感器重新定位到ER- pm连接区域的离散点上，这导致Ca2+通道的耦合，从而启动SOCE。然而，调控STIM1活性的机制仍然知之甚少。在这里，我们对STIM1进行了亲和纯化，并发现了作为STIM1结合伙伴的ER膜蛋白复合物1 （EMC1）。我们发现这种相互作用通过STIM1的腔内区域发生在内质网。储存耗尽后，EMC1不再聚集在PM附近，这表明它的分布与STIM1不同。用小干扰RNA敲低EMC1导致SOCE显著降低。因此，这些研究结果表明，EMC1是SOCE的积极调节因子。
Store-operated calcium entry (SOCE) is the process by which the emptying of endoplasmic reticulum (ER) Ca2+ stores causes an influx of Ca2+ across the plasma membrane (PM). It is the major Ca2+ influx pathway in nonexcitable cells and has a wide array of physiological functions. Upon store depletion, stromal interaction molecule 1 (STIM1), an ER calcium sensor relocates into discrete puncta at the ER-PM junction region, which results in the coupling of Ca2+ channels to initiate SOCE. However, the mechanism regulating STIM1 activity remains poorly understood. Here, we performed affinity purification of STIM1 and uncovered ER membrane protein complex 1 (EMC1) as an STIM1 binding partner. We showed that this interaction occurred in the ER through the intraluminal region of STIM1. After store depletion, EMC1 does not cluster adjacent to the PM, which suggests that it is distributed differently from STIM1. EMC1 knockdown with small interfering RNA resulted in a marked decrease in SOCE. Thus, these findings suggest that EMC1 functions as a positive regulator of SOCE.[GRAPHICS].