論文 - 詳細
| RRC ID | 88003 |
|---|---|
| 著者 | Rossi L, Amoako K, Busack I, Golinelli L, Courtney A, Besseling J, Schafer W, Beets I, Bringmann H. |
| タイトル | The neuropeptide FLP-11 induces and self-inhibits sleep through the receptor DMSR-1 in Caenorhabiditis elegans. |
| ジャーナル | Curr Biol |
| Abstract |
Sleep is caused by the depolarization of sleep-active neurons, which secrete gamma-aminobutyric acid (GABA) and neuropeptides such as conserved RFamide (c-terminal Arg-Phe-NH2 motif) neuropeptides to dictate when an organism falls asleep and when it wakes up.1,2,3,4,5,6,7,8,9,10 However, the mechanisms by which neurotransmission from sleep-active neurons induces sleep and determines the duration of sleep remain poorly understood. Sleep in Caenorhabditis elegans crucially requires the single sleep-active RIS neuron, which induces sleep via the release of FLP-11 RFamide neuropeptides.8,11 However, how RIS and FLP-11 control sleep is not well understood, as the receptor through which FLP-11 acts has yet to be identified. In this study, we discovered that RIS and FLP-11 control sleep through the Gi/o-protein coupled receptor DroMyoSuppressin receptor related 1 (DMSR-1).12,13 Using cell-specific knockdowns,14 we demonstrate that dmsr-1 induces sleep by acting in cholinergic neurons downstream of RIS activation. Pharmacological intervention indicates that inhibiting cholinergic signaling is necessary for sleep. Consistently, DMSR-1 expression in cholinergic neurons is essential for core sleep functions, including protective gene expression and survival. In contrast, we found that dmsr-1 in RIS mediates negative feedback control during sleep that limits RIS calcium activation and the duration of sleep. Consequently, dmsr-1 in RIS inhibits protective gene expression and survival. Thus, DMSR-1 controls both the initiation and limitation of sleep, effectively coupling sleep induction with a sleep-stop signal. RFamide neuropeptide-GPCR signaling might underlie similar dual mechanisms of sleep control in other species, and self-inhibition of sleep-active neurons might represent a conserved mechanism for limiting the duration of sleep. VIDEO ABSTRACT. |
| 巻・号 | 35(9) |
| ページ | 2183-2194.e10 |
| 公開日 | 2025-5-5 |
| DOI | 10.1016/j.cub.2025.03.039 |
| PII | S0960-9822(25)00355-0 |
| PMID | 40273913 |
| PMC | PMC7617803 |
| MeSH | Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / physiology Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Neurons / metabolism Neurons / physiology Neuropeptides* / genetics Neuropeptides* / metabolism Receptors, G-Protein-Coupled* / genetics Receptors, G-Protein-Coupled* / metabolism Sleep* / physiology |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 26 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1872 tm2706 tm2427 tm1782 |