A non-canonical role for UPR ER during heat stress in C. elegans.
Organisms rely on coordinated stress responses to maintain cellular homeostasis. Perhaps thebest-known example of multiple stress inputs converging onto a single response is theintegrated stress response (ISR), which reduces global translation under various stressedconditions to reduce the protein folding burden of the cell. Similarly, most stress responsesgenerally involve coordination of additional protein homeostasis (proteostasis) pathways,including increased expression of chaperones to refold proteins, as well as activation ofclearance mechanisms, such as autophagy and the ubiquitin proteosome system. Our studyinvestigates how heat stress can influence coordinated activation of both cytosolic and ERchaperones, exploring bidirectional cross talk between canonical activators of the cytosolic heat-shock response (HSR) and the unfolded protein response of the ER (UPR ER ). Using robusttranscriptional reporters in the C. elegans model system, we explore a non-canonical activationof the UPR ER under heat stress by the coordinated effects of XBP-1 and HSF-1. We furtherinvestigate inter tissue communications of stress whereby neuronal or glial activation of theUPR ER can result in heterotypic enhancement of the HSR in peripheral and can increasethermotolerance. This work highlights the complex convergence of cellular stress responses, aphenomenon that may reflect a general strategy wherein localized stress can activate numerousproteostasis pathways to prevent whole cell and whole organism damage.