ER proteostasis regulators cell-non-autonomously control sleep

Taizo Kawano, Mitsuaki Kashiwagi, Mika Kanuka, Chung Kuan Chen, Shinnosuke Yasugaki, Sena Hatori, Shinichi Miyazaki, Kaeko Tanaka, Hidetoshi Fujita, Toshiro Nakajima, Masashi Yanagisawa, Yoshimi Nakagawa, Yu Hayashi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Article number112267
JournalCell Reports
Volume42
Issue number3
DOIs
StatePublished - Mar 28 2023

Keywords

  • C. elegans
  • CP: Cell biology
  • CP: Neuroscience
  • EGFR
  • cell non-autonomous
  • endoplasmic reticulum-associated degradation
  • proteostasis
  • sleep

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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