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Highlights • XBP-1s drives a distinct transcriptional program in C. elegans neurons • Neuronal XBP-1s requires tyramine synthesis to induce intestinal UPR activation • XBP-1s expression in RIM and RIC neurons drives cell non-autonomous UPR activation • Neuronal XBP-1s changes behavior and reproduction, dependent on tyramine synthesis Summary In C.
Highlights • Xbp-1s expressed in the neurons or intestine of C. elegans improves proteostasis • Neuronal xbp-1s drives expression of lysosomal genes in the intestine • Intestinal lysosomes show enhanced acidity and activity upon xbp-1s expression • Lysosome function is required for xbp-1s to increase proteostasis and longevity Summary The unfolded protein response of the endoplasmic reticulum (UPRER) is a crucial mediator of secretory pathway homeostasis.
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