The RFamide receptor DMSR-1 regulates stress-induced sleep in C. elegans
Michael J Iannacone,
Isabel Beets,
Lindsey E Lopes,
Matthew A Churgin,
Christopher Fang-Yen,
Matthew D Nelson,
Liliane Schoofs,
David M Raizen
Affiliations
Michael J Iannacone
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
Isabel Beets
Department of Biology, Katholieke Universiteit Leuven, Leuven, Belgium
Lindsey E Lopes
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
Matthew A Churgin
Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, United States
Christopher Fang-Yen
Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, United States
Matthew D Nelson
Department of Biology, Saint Joseph’s University, Philadelphia, United States
Liliane Schoofs
Department of Biology, Katholieke Universiteit Leuven, Leuven, Belgium
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States; Center for Sleep and Circadian Neurobiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States
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.
