期刊
CURRENT BIOLOGY
卷 31, 期 3, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.cub.2020.10.076
关键词
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资金
- National Institutes of Health Office of Research Infrastructure Programs [P40 OD010440]
- Max Planck Society (Max Planck Research Group ''Sleep and Waking'')
- European Research Council [637860]
- French National Research Agency [ANR-16-CE15-0001-01]
- Investissements d'Avenir French government program [ANR-16-CONV-0001]
- Excellence Initiative of Aix-Marseille University -A*MIDEX
- CNRS
- Aix-Marseille University
- INSERM
- European Research Council (ERC) [637860] Funding Source: European Research Council (ERC)
- Agence Nationale de la Recherche (ANR) [ANR-16-CE15-0001] Funding Source: Agence Nationale de la Recherche (ANR)
In C. elegans, a protein called NAS-38 promotes sleep during the molting process by activating immune pathways that lead to the expression of antimicrobial peptide genes. This signaling mechanism may also exist in other animals, including humans, to regulate sleep in response to injury and infection.
Wounding and infection trigger a protective innate immune response that includes the production of antimicrobial peptides in the affected tissue as well as increased sleep. Little is known, however, how peripheral wounds or innate immunity signal to the nervous system to increase sleep. We found that, during C. elegans larval molting, an epidermal tolloid/bone morphogenic protein (BMP)-1-like protein called NAS-38 promotes sleep. NAS-38 is negatively regulated by its thrombospondin domain and acts through its astacin protease domain to activate p38 mitogen-activated protein (MAP)/PMK-1 kinase and transforming growth factor beta (TGF-beta)-SMAD/SMA-3-dependent innate immune pathways in the epidermis that cause STAT/STA-2 and SLC6 (solute carrier)/SNF-12-dependent expression of antimicrobial peptide (AMP) genes. We show that more than a dozen epidermal AMPs act as somnogens, signaling across tissues to promote sleep through the sleep-active RIS neuron. In the adult, epidermal injury activates innate immunity and turns up AMP production to trigger sleep, a process that requires epidermal growth factor receptor (EGFR) signaling that is known to promote sleep following cellular stress. We show for one AMP, neuropeptide-like protein (NLP)-29, that it acts through the neuropeptide receptor NPR-12 in locomotion-controlling neurons that are presynaptic to RIS and that depolarize this neuron to induce sleep. Sleep in turn increases the chance of surviving injury. Thus, we found a novel mechanism by which peripheral wounds signal to the nervous system to increase protective sleep. Such a cross-tissue somnogen-signaling function of AMPs might also boost sleep in other animals, including humans.
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