期刊
FASEB JOURNAL
卷 33, 期 8, 页码 8892-8904出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201802626R
关键词
calcium; calsequestrin; ER stress; sarcoplasmic reticulum
资金
- Canadian Institutes of Health Research [MOP-15291, MOP-15415, MOP-53050, PS-153325]
- SynAD Program (University of Alberta)
- U.S. National Institutes of Health, National Heart, Lung and Blood Institute Grant [R35-HL144980]
- National Natural Science Foundation of China [31871420, 81602448]
- Heart and Stroke Foundation of Alberta, Northwest Territories and Nunavut
- Natural Sciences Engineering Research Council of Canada
- Heart and Stroke Foundation Chair in Cardiovascular Research
- Canadian Institutes of Health [MOP-15291, PS-153325]
The endoplasmic reticulum (ER) plays a central role in cellular stress responses via mobilization of ER stress coping responses, such as the unfolded protein response (UPR). The inositol-requiring 1 alpha (IRE1 alpha) 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 Ca2+ storage, release, and uptake to control muscle excitation-contraction coupling. Here, we describe 2 distinct pools of IRE1 alpha 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 IRE1 alpha, inhibiting its dimerization. This novel interaction of IRE1 alpha with calsequestrin, one of the highly abundant Ca2+ 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 IRE1 alpha in cardiac and skeletal muscle cells.
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