Cell Structure and Function
Online ISSN : 1347-3700
Print ISSN : 0386-7196
ISSN-L : 0386-7196
Multiple Ways for Stress Sensing and Regulation of the Endoplasmic Reticulum-stress Sensors
Quynh Giang LeYukio Kimata
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2021 Volume 46 Issue 1 Pages 37-49


Dysfunction of the endoplasmic reticulum (ER), so-called ER stress, is accompanied with accumulation of unfolded proteins in the ER. Eukaryotic cells commonly have an ER-located transmembrane protein, Ire1, which triggers cellular protective events against ER stress. In animal cells, PERK and ATF6 also initiate the ER-stress response. As a common strategy to control the activity of these ER-stress sensors, an ER-resident molecular chaperone, BiP, serves as their negative regulator, and dissociates from them in response to ER stress. Although it sounds reasonable that unfolded proteins and Ire1 compete for BiP association, some publications argue against this competition model. Moreover, yeast Ire1 (and possibly also the mammalian major Ire1 paralogue IRE1α) directly detects ER-accumulated unfolded proteins, and subsequently oligomerizes for its further activation. Apart from protein misfolding, the saturation of membrane phospholipids is another outcome of ER-stressing stimuli, which is sensed by the transmembrane domain of Ire1. This review describes the canonical and up-to-date insights concerning stress-sensing and regulatory mechanisms of yeast Ire1 and metazoan ER-stress sensors.

Key words: endoplasmic reticulum, stress, unfolded protein response, molecular chaperone

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© 2021 The Author(s) CC-BY 4.0 (Submission before October 2016: Copyright © Japan Society for Cell Biology)

Copyright: ©2021 The Author(s). This is an open access article distributed under the terms of the Creative Commons BY (Attribution) License (https://creativecommons.org/licenses/by/4.0/legalcode), which permits the unrestricted distribution, reproduction and use of the article provided the original source and authors are credited.
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