Imaging of single cell responses to ER stress indicates that the relative dynamics of IRE1/XBP1 and PERK/ATF4 signalling rather than a switch between signalling branches determine cell survival.

ABSTRACT: An accumulation of misfolded proteins in the endoplasmic reticulum (ER) triggers the unfolded protein response (UPR) mediated via the activation of three transmembrane proteins IRE1, PERK and ATF6. Signalling through these proteins is aimed at enhancing the ER folding capacity and reducing the folding load. If these processes fail to re-establish protein homeostasis within the ER, then cell death prevails via apoptosis. How the shift from pro-survival to pro-apoptotic signalling is regulated remains unclear with both IRE1 and PERK signalling associated with pro-survival as well as pro-apoptotic signalling. To investigate the temporal activation of IRE1 and PERK in live cells and their relationship to cellular fate, we devised single cell reporters for both ER stress signalling branches. SH

SUBMITTER: Walter F 

PROVIDER: S-EPMC4532775 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature