| RRC ID |
76207
|
| 著者 |
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.
|
| タイトル |
ER proteostasis regulators cell-non-autonomously control sleep.
|
| ジャーナル |
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.
|
| 巻・号 |
42(3)
|
| ページ |
112267
|
| 公開日 |
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
|
| リソース情報 |
| 線虫 |
tm4397
tm1340
tm1944 |
| ヒト・動物細胞 |
293T(RCB2202) |
