RRC ID 76207
Author Kawano T, Kashiwagi M, Kanuka M, Chen CK, Yasugaki S, Hatori S, Miyazaki S, Tanaka K, Fujita H, Nakajima T, Yanagisawa M, Nakagawa Y, Hayashi Y.
Title ER proteostasis regulators cell-non-autonomously control sleep.
Journal Cell Rep
Abstract Sleep is regulated by peripheral tissues under fatigue. The molecular pathways in peripheral cells that trigger systemic sleep-related signals, however, are unclear. Here, a forward genetic screen in C. elegans identifies 3 genes that strongly affect sleep amount: sel-1, sel-11, and mars-1. sel-1 and sel-11 encode endoplasmic reticulum (ER)-associated degradation components, whereas mars-1 encodes methionyl-tRNA synthetase. We find that these machineries function in non-neuronal tissues and that the ER unfolded protein response components inositol-requiring enzyme 1 (IRE1)/XBP1 and protein kinase R-like ER kinase (PERK)/eukaryotic initiation factor-2α (eIF2α)/activating transcription factor-4 (ATF4) participate in non-neuronal sleep regulation, partly by reducing global translation. Neuronal epidermal growth factor receptor (EGFR) signaling is also required. Mouse studies suggest that this mechanism is conserved in mammals. Considering that prolonged wakefulness increases ER proteostasis stress in peripheral tissues, our results suggest that peripheral ER proteostasis factors control sleep homeostasis. Moreover, based on our results, peripheral tissues likely cope with ER stress not only by the well-established cell-autonomous mechanisms but also by promoting the individual's sleep.
Volume 42(3)
Pages 112267
Published 2023-3-28
DOI 10.1016/j.celrep.2023.112267
PII S2211-1247(23)00278-4
PMID 36924492
MeSH Activating Transcription Factor 4 / genetics Activating Transcription Factor 4 / metabolism Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Endoplasmic Reticulum Stress / physiology Mammals / metabolism Mice Proteostasis* Signal Transduction Unfolded Protein Response eIF-2 Kinase / genetics eIF-2 Kinase / metabolism
C.elegans tm4397 tm1340 tm1944
Human and Animal Cells 293T(RCB2202)