Heat stress reveals bidirectional crosstalk between the heat shock response and the UPRER in C. elegans

Perhaps the best-known example of multiple stress inputs converging onto a single response is the integrated stress response (ISR), which reduces global translation under various stressed conditions to reduce the protein folding burden of the cell. Similarly, most stress responses generally involve coordination of additional protein homeostasis (proteostasis) pathways, including increased expression of chaperones to refold proteins, as well as activation of clearance mechanisms, such as autophagy and the ubiquitin proteosome system.

Our study investigates how heat stress can influence coordinated activation of both cytosolic and ER chaperones, exploring bidirectional cross talk between canonical activators of the cytosolic heat-shock response (HSR) and the unfolded protein response of the ER (UPRER). Using robust transcriptional reporters in the C. elegans model system, we explore a non-canonical activation of the UPRER under heat stress by the coordinated effects of XBP-1 and HSF-1.