Kawata Kazuhiko, Baba Akemi, Shiota Masayuki, Wanibuchi Hideki, Baba Yoshihiro
Division of Immunology and Genome Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Department of Molecular Biology of Medicine, Osaka City University Medical School, 1-4-3 Asahi-cho, Abeno-ku, Osaka 545-8585, Japan.
J Biochem. 2021 Dec 4;170(4):483-488. doi: 10.1093/jb/mvab063.
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.
钙库操纵性钙内流（SOCE）是指内质网（ER）钙库排空导致钙离子通过质膜（PM）内流的过程。它是不可兴奋细胞中主要的钙离子内流途径，具有广泛的生理功能。在钙库耗竭时，内质网钙传感器基质相互作用分子1（STIM1）重新定位于内质网-质膜交界区域的离散点状结构中，从而导致钙离子通道偶联以启动SOCE。然而，调节STIM1活性的机制仍知之甚少。在此，我们对STIM1进行了亲和纯化，并发现内质网膜蛋白复合物1（EMC1）是STIM1的结合伴侣。我们表明这种相互作用通过STIM1的腔内区域在内质网中发生。钙库耗竭后，EMC1不会聚集在质膜附近，这表明它与STIM1的分布不同。用小干扰RNA敲低EMC1会导致SOCE显著降低。因此，这些发现表明EMC1作为SOCE的正向调节因子发挥作用。
