Sensing Endoplasmic Reticulum Stress

This chapter provides an overview of our present understanding of mechanisms of sensing protein folding status and endoplasmic reticulum (ER) stress in eukaryotic cells. The ER folds and matures most secretory and transmembrane proteins. Mis- or unfolded proteins are sensed by specialized ER stress sensors, such as IRE1, PERK and ATF6, which initiate several cellular responses and signaling pathways to restore ER homeostasis. These intracellular signaling events are called the unfolded protein response (UPR). Here we focus on how ER stress and protein folding status in the ER are sensed by the ER stress sensors by summarizing results from recent structural, biochemical and genetic approaches.