University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Anatomy II, Cologne, Germany.
University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Anatomy II, Cologne, Germany.
J Biol Chem. 2022 Jul;298(7):102061. doi: 10.1016/j.jbc.2022.102061. Epub 2022 May 21.
The concentration of Ca in the endoplasmic reticulum (ER) is critically important for maintaining its oxidizing environment as well as for maintaining luminal ATP levels required for chaperone activity. Therefore, local luminal Ca concentrations and the dynamic Ca flux between the different subcellular compartments are tightly controlled. Influx of Ca into the ER is enabled by a reductive shift, which opens the sarcoendoplasmic reticulum calcium transport ATPase pump, building the Ca gradient across the ER membrane required for ATP import. Meanwhile, Ca leakage from the ER has been reported to occur via the Sec61 translocon following protein translocation. In this review, we provide an overview of the complex regulation of Ca homeostasis, Ca flux between subcellular compartments, and the cellular stress response (the unfolded protein response) induced upon dysregulated luminal Ca metabolism. We also provide insight into the structure and gating mechanism at the Sec61 translocon and examine the role of ER-resident cochaperones in assisting the central ER-resident chaperone BiP in the control of luminal Ca concentrations.
内质网 (ER) 中的 Ca 浓度对于维持其氧化环境以及维持腔内 ATP 水平以维持伴侣活性至关重要。因此，局部腔内 Ca 浓度和不同亚细胞区室之间的动态 Ca 通量受到严格控制。内质网中的 Ca 内流是通过还原性转变实现的，该转变打开了肌浆内质网钙转运 ATP 酶泵，在内质网膜上建立了用于 ATP 导入的 Ca 梯度。同时，据报道，内质网中的 Ca 泄漏是在蛋白质易位后通过 Sec61 转位体发生的。在这篇综述中，我们概述了 Ca 动态平衡、亚细胞区室之间的 Ca 通量以及细胞应激反应（未折叠蛋白反应）的复杂调节，这些反应是由内质网腔中 Ca 代谢失调引起的。我们还深入了解了 Sec61 转位体的结构和门控机制，并研究了 ER 驻留伴侣蛋白在协助中央 ER 驻留伴侣蛋白 BiP 控制腔内 Ca 浓度方面的作用。
