Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada.
National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Hubei University of Technology, Wuhan, China.
FASEB J. 2019 Aug;33(8):8892-8904. doi: 10.1096/fj.201802626R. Epub 2019 May 3.
The endoplasmic reticulum (ER) plays a central role in cellular stress responses mobilization of ER stress coping responses, such as the unfolded protein response (UPR). The inositol-requiring 1α (IRE1α) is an ER stress sensor and component of the UPR. Muscle cells also have a well-developed and highly subspecialized membrane network of smooth ER called the sarcoplasmic reticulum (SR) surrounding myofibrils and specialized for Ca storage, release, and uptake to control muscle excitation-contraction coupling. Here, we describe 2 distinct pools of IRE1α in cardiac and skeletal muscle cells, one localized at the perinuclear ER and the other at the junctional SR. We discovered that, at the junctional SR, calsequestrin binds to the ER luminal domain of IRE1α, inhibiting its dimerization. This novel interaction of IRE1α with calsequestrin, one of the highly abundant Ca handling proteins at the junctional SR, provides new insights into the regulation of stress coping responses in muscle cells.-Wang, Q., Groenendyk, J., Paskevicius, T., Qin, W., Kor, K. C., Liu, Y., Hiess, F., Knollmann, B. C., Chen, S. R. W., Tang, J., Chen, X.-Z., Agellon, L. B., Michalak, M. Two pools of IRE1α in cardiac and skeletal muscle cells.
内质网 (ER) 在细胞应激反应中起着核心作用，它可以调动 ER 应激应对反应，如未折叠蛋白反应 (UPR)。肌醇需求酶 1α (IRE1α) 是 ER 应激传感器和 UPR 的组成部分。肌肉细胞还具有发达且高度专业化的肌浆内质网 (SR) 膜网络，称为肌浆网 (SR)，围绕肌原纤维并专门用于 Ca 储存、释放和摄取，以控制肌肉兴奋-收缩偶联。在这里，我们描述了心脏和骨骼肌细胞中 2 种不同的 IRE1α 池，一种位于核周 ER，另一种位于连接 SR。我们发现，在连接 SR 上，钙结合蛋白与 IRE1α 的 ER 腔域结合，抑制其二聚化。IRE1α 与钙结合蛋白（连接 SR 上高度丰富的 Ca 处理蛋白之一）的这种新型相互作用为肌肉细胞中应激应对反应的调节提供了新的见解。-Wang, Q., Groenendyk, J., Paskevicius, T., Qin, W., Kor, K. C., Liu, Y., Hiess, F., Knollmann, B. C., Chen, S. R. W., Tang, J., Chen, X.-Z., Agellon, L. B., Michalak, M. 心脏和骨骼肌细胞中的两种 IRE1α 池。
