Rhythmic control of activity and sleep by class B1 GPCRs

Crit Rev Biochem Mol Biol. 2015 Jan-Feb;50(1):18-30. doi: 10.3109/10409238.2014.985815. Epub 2014 Nov 20.


Members of the class B1 family of G-protein coupled receptors (GPCRs) whose ligands are neuropeptides have been implicated in regulation of circadian rhythms and sleep in diverse metazoan clades. This review discusses the cellular and molecular mechanisms by which class B1 GPCRs, especially the mammalian VPAC2 receptor and its functional homologue PDFR in Drosophila and C. elegans, regulate arousal and daily rhythms of sleep and wake. There are remarkable parallels in the cellular and molecular roles played by class B1 intercellular signaling pathways in coordinating arousal and circadian timekeeping across multiple cells and tissues in these very different genetic model organisms.

Keywords: Circadian; Drosophila; G-protein coupled receptor; neuropeptides; sleep; suprachiasmatic nucleus.

Publication types

  • Review

MeSH terms

  • Animals
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins / metabolism*
  • Circadian Rhythm / physiology*
  • Drosophila / physiology
  • Drosophila Proteins / metabolism*
  • Humans
  • Phylogeny
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Sleep / physiology*


  • Caenorhabditis elegans Proteins
  • Drosophila Proteins
  • PDFR protein, Drosophila
  • Receptors, G-Protein-Coupled