The RFamide receptor DMSR-1 regulates stress-induced sleep in C. elegans

Elife. 2017 Jan 17;6:e19837. doi: 10.7554/eLife.19837.

Abstract

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.

Keywords: C. elegans; GPCR; RFamide; neuropeptides; neuroscience; sickness; sleep.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / metabolism*
  • Gene Expression Regulation*
  • Neuropeptides / metabolism*
  • Receptors, Peptide / metabolism*
  • Sleep*
  • Stress, Physiological*

Substances

  • Caenorhabditis elegans Proteins
  • Neuropeptides
  • Receptors, Peptide
  • arginylphenylalaninamide