ArticleNature communications2024
Sleep drive is coupled to tissue damage via shedding of Caenorhabditis elegans EGFR ligand SISS-1.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
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- A screen for stress-induced sleep genes in Caenorhabditis elegans reveals a role for glutamate signaling.Genetics · 2026Article
- KIN-29 SIK regulates stress-induced sleep through mitochondrial redox signaling.bioRxiv : the preprint server for biology · 2026Article
- A genetically encoded sensor of ionic stress links cellular proton dynamics to sleep.Science advances · 2026Article
- Article
- A genetically encoded ionic-stress sensor reveals protons as a sleep driver.bioRxiv : the preprint server for biology · 2026Article
- Peripheral modulation of Pumilio in intestinal stem cells and the corpus allatum affects sleep latency in Drosophila.PloS one · 2026Article
- Expression of themicroPublication biology · 2026Article
- Characterization of the Immunoglobulin Domain ofmicroPublication biology · 2026Article
- Imaging cellular activity simultaneously across all organs of a vertebrate reveals body-wide circuits.bioRxiv : the preprint server for biology · 2025Article
- Predation by nematode-trapping fungus triggers mechanosensory-dependent quiescence iniScience · 2025Article
- The immunoglobulin domain ofmicroPublication biology · 2025Article
- The Immunoglobulin Domain of SISS-1/EGF is Required for its Function.microPublication biology · 2025Article
- IGEG-2 is amicroPublication biology · 2025Article
- Indole induces acute paralysis followed by compensatory stress-induced sleep.microPublication biology · 2025Article
- Egg laying during stress-induced sleep ofmicroPublication biology · 2025Article
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Authors and funding
5 authors.
Funding
Abstract
The benefits of sleep extend beyond the nervous system. Peripheral tissues impact sleep regulation, and increased sleep is observed in response to damaging conditions, even those that selectively affect non-neuronal cells. However, the 'sleep need' signal released by stressed tissues is not known. Sleep in the nematode C. elegans is independent of circadian cues and can be triggered rapidly by damaging conditions. This stress-induced sleep is mediated by neurons that require the Epidermal Growth Factor Receptor (EGFR) for their sleep-promoting function, but the only known C. elegans EGFR ligand, LIN-3, is not required for sleep. Here we describe SISS-1 (stress-induced sleepless), an EGF family ligand that is required for stress-induced sleep. We show that SISS-1 overexpression induces sleep in an EGFR-dependent, sleep neuron-dependent manner. We find that SISS-1 undergoes stress-responsive shedding by the ADM-4/ADAM17 metalloprotease, and that the ADM-4 site of action depends on the tissue specificity of the stressor. Our findings support a model in which SISS-1 is released from damaged tissues to activate EGFR in sleep neurons, identifying a molecular link between cellular stress and organismal sleep drive. Our data also point to a mechanism insulating this sleep signal from EGFR-mediated signaling during development.
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