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ER Ca2+ overload activates the IRE1α signaling and promotes cell survival.
- Source :
-
Cell & Bioscience . 7/3/2023, Vol. 13 Issue 1, p1-19. 19p. - Publication Year :
- 2023
-
Abstract
- Background: Maintaining homeostasis of Ca2+ stores in the endoplasmic reticulum (ER) is crucial for proper Ca2+ signaling and key cellular functions. Although Ca2+ depletion has been known to cause ER stress which in turn activates the unfolded protein response (UPR), how UPR sensors/transducers respond to excess Ca2+ when ER stores are overloaded remain largely unclear. Results: Here, we report for the first time that overloading of ER Ca2+ can directly sensitize the IRE1α-XBP1 axis. The overloaded ER Ca2+ in TMCO1-deficient cells can cause BiP dissociation from IRE1α, promote the dimerization and stability of the IRE1α protein, and boost IRE1α activation. Intriguingly, attenuation of the over-activated IRE1α-XBP1s signaling by a IRE1α inhibitor can cause a significant cell death in TMCO1-deficient cells. Conclusions: Our data establish a causal link between excess Ca2+ in ER stores and the selective activation of IRE1α-XBP1 axis, underscoring an unexpected role of overload of ER Ca2+ in IRE1α activation and in preventing cell death. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20453701
- Volume :
- 13
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Cell & Bioscience
- Publication Type :
- Academic Journal
- Accession number :
- 164679439
- Full Text :
- https://doi.org/10.1186/s13578-023-01062-y