Dynamic changes in oligomeric complexes of UPR sensors induced by misfolded proteins in the ER

Abstract

The endoplasmic reticulum (ER) localized unfolded protein response (UPR) sensors, IRE1α, 3 PERK, and ATF6α, are activated upon accumulation of misfolded proteins caused by ER 4 stress. It is debated whether these UPR sensors are activated either by the release of their 5 negative regulator BiP chaperone or directly binding to misfolded proteins during ER stress. 6Here we simultaneously examined oligomerization and activation of all three endogenous 7 UPR sensors. We found that UPR sensors existed as preformed oligomers even in unstressed