Tyramine Acts Downstream of Neuronal XBP-1s to Coordinate Inter-tissue UPR^ER Activation and Behavior in C. elegans.

ABSTRACT: In C. elegans, expression of the UPR^ER transcription factor xbp-1s in neurons cell non-autonomously activates the UPR^ER in the intestine, leading to enhanced proteostasis and lifespan. To better understand this signaling pathway, we isolated neurons from animals expressing neuronal xbp-1s for transcriptomic analysis, revealing a striking remodeling of transcripts involved in neuronal signaling. We then identified signaling molecules required for cell non-autonomous intestinal UPR^ER activation, including the biogenic amine tyramine. Expression of xbp-1s in just two pairs of neurons that synthesize tyramine, the RIM and RIC interneurons, induced intestinal UPR^ER activation and extended longevity, and exposure to stress led to splicing and activatio

SUBMITTER: Ozbey NP 

PROVIDER: S-EPMC7758879 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature