Identification of SLEEPLESS, a sleep-promoting factor

Science. 2008 Jul 18;321(5887):372-6. doi: 10.1126/science.1155942.


Sleep is an essential process conserved from flies to humans. The importance of sleep is underscored by its tight homeostatic control. Through a forward genetic screen, we identified a gene, sleepless, required for sleep in Drosophila. The sleepless gene encodes a brain-enriched, glycosylphosphatidylinositol-anchored protein. Loss of SLEEPLESS protein caused an extreme (>80%) reduction in sleep; a moderate reduction in SLEEPLESS had minimal effects on baseline sleep but markedly reduced the amount of recovery sleep after sleep deprivation. Genetic and molecular analyses revealed that quiver, a mutation that impairs Shaker-dependent potassium current, is an allele of sleepless. Consistent with this finding, Shaker protein levels were reduced in sleepless mutants. We propose that SLEEPLESS is a signaling molecule that connects sleep drive to lowered membrane excitability.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Behavior, Animal
  • Brain / metabolism
  • Cell Membrane / metabolism
  • DNA Transposable Elements
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology*
  • Female
  • Genes, Insect*
  • Glycosylphosphatidylinositols
  • Homeostasis
  • Longevity
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Membrane Proteins / physiology*
  • Models, Animal*
  • Molecular Sequence Data
  • Mutation
  • Phenotype
  • Shaker Superfamily of Potassium Channels / physiology
  • Signal Transduction
  • Sleep Deprivation
  • Sleep* / genetics
  • Sleep* / physiology
  • Transgenes


  • DNA Transposable Elements
  • Drosophila Proteins
  • Glycosylphosphatidylinositols
  • Membrane Proteins
  • Qvr protein, Drosophila
  • Sh protein, Drosophila
  • Shaker Superfamily of Potassium Channels