SIFamide and SIFamide receptor defines a novel neuropeptide signaling to promote sleep in Drosophila

Mol Cells. 2014 Apr;37(4):295-301. doi: 10.14348/molcells.2014.2371. Epub 2014 Mar 21.


SIFamide receptor (SIFR) is a Drosophila G protein-coupled receptor for the neuropeptide SIFamide (SIFa). Although the sequence and spatial expression of SIFa are evolutionarily conserved among insect species, the physiological function of SIFa/SIFR signaling remains elusive. Here, we provide genetic evidence that SIFa and SIFR promote sleep in Drosophila. Either genetic ablation of SIFa-expressing neurons in the pars intercerebralis (PI) or pan-neuronal depletion of SIFa expression shortened baseline sleep and reduced sleep-bout length, suggesting that it caused sleep fragmentation. Consistently, RNA interference- mediated knockdown of SIFR expression caused short sleep phenotypes as observed in SIFa-ablated or depleted flies. Using a panel of neuron-specific Gal4 drivers, we further mapped SIFR effects to subsets of PI neurons. Taken together, these results reveal a novel physiological role of the neuropeptide SIFa/SIFR pathway to regulate sleep through sleep-promoting neural circuits in the PI of adult fly brains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila*
  • Female
  • Male
  • Neurons / physiology*
  • Neuropeptides / metabolism*
  • Pituitary Gland, Intermediate / pathology*
  • RNA, Small Interfering / genetics
  • Receptors, Neuropeptide / genetics
  • Receptors, Neuropeptide / metabolism*
  • Signal Transduction / genetics
  • Sleep Deprivation / genetics
  • Sleep Deprivation / metabolism*
  • Sleep* / genetics
  • Transcription Factors / genetics


  • Drosophila Proteins
  • GAL4 protein, Drosophila
  • Neuropeptides
  • RNA, Small Interfering
  • Receptors, Neuropeptide
  • SIFamide receptor, Drosophila
  • SIFamide, Drosophila
  • Transcription Factors