In response to environments that cause cellular stress, animals engage in sleep behavior that facilitates recovery from the stress. In Caenorhabditis elegans, stress-induced sleep (SIS) is regulated by cytokine activation of the ALA neuron, which releases FLP-13 neuropeptides characterized by an amidated arginine-phenylalanine (RFamide) C-terminus motif. By performing an unbiased genetic screen for mutants that impair the somnogenic effects of FLP-13 neuropeptides, we identified the gene dmsr-1, which encodes a G-protein coupled receptor similar to an insect RFamide receptor. DMSR-1 is activated by FLP-13 peptides in cell culture, is required for SIS in vivo, is expressed non-synaptically in several wake-promoting neurons, and likely couples to a Gi/o heterotrimeric G-protein. Our data expand our understanding of how a single neuroendocrine cell coordinates an organism-wide behavioral response, and suggest that similar signaling principles may function in other organisms to regulate sleep during sickness.
Bibliographical noteFunding Information:
We thank Jessie Zhou, Mark Nessel, and Eve Phelps for technical assistance, Hilary Debardeleben for showing that ultraviolet light causes SIS, and Gregg Artiushin for demonstrating feasibility of flp-13(OE) suppressor screen by isolating the first mutant. We thank Raizen lab members for discussions and comments on this manuscript. A HisCl plasmid was provided by Cori Bargmann. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40-OD010440). This research was supported in part by the National Institutes of Health (R01-NS088432, R21-NS091500, and P30-ES013508), the European Research Council (ERC-2013-ADG-340318), and the Research Foundation Flanders (FWO). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NINDS, NIEHS, NIH, ERC, or the FWO.
© Iannacone et al.
ASJC Scopus subject areas
- Immunology and Microbiology(all)
- Biochemistry, Genetics and Molecular Biology(all)