Abstract

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. It is the major Ca²⁺ influx pathway in non-excitable 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-plasma membrane 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 a 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 plasma membrane, 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.

中文翻译：

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ER 膜蛋白复合物 1 与 STIM1 相互作用并调节钙池操作的 Ca2+ 进入

摘要

钙池操作性钙进入 (SOCE) 是内质网 (ER) Ca ²⁺库的排空导致 Ca ²⁺跨质膜流入的过程。它是非兴奋性细胞中主要的 Ca ²⁺流入途径，具有多种生理功能。储存耗尽后，基质相互作用分子 1 (STIM1)，一种内质网钙传感器重新定位到内质网-质膜连接区的离散点中，导致 Ca ²⁺的耦合启动 SOCE 的渠道。然而，调节 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，并发现了内质网膜蛋白复合物 1 (EMC1) 作为 STIM1 结合伙伴。我们表明这种相互作用通过 STIM1 的腔内区域发生在 ER 中。储存耗尽后，EMC1 不会在质膜附近聚集，这表明它的分布与 STIM1 不同。使用小干扰 RNA 敲低 EMC1 导致 SOCE 显着减少。因此，这些发现表明 EMC1 作为 SOCE 的正调节器发挥作用。