Reduced sleep in Drosophila Shaker mutants

Nature. 2005 Apr 28;434(7037):1087-92. doi: 10.1038/nature03486.

Abstract

Most of us sleep 7-8 h per night, and if we are deprived of sleep our performance suffers greatly; however, a few do well with just 3-4 h of sleep-a trait that seems to run in families. Determining which genes underlie this phenotype could shed light on the mechanisms and functions of sleep. To do so, we performed mutagenesis in Drosophila melanogaster, because flies also sleep for many hours and, when sleep deprived, show sleep rebound and performance impairments. By screening 9,000 mutant lines, we found minisleep (mns), a line that sleeps for one-third of the wild-type amount. We show that mns flies perform normally in a number of tasks, have preserved sleep homeostasis, but are not impaired by sleep deprivation. We then show that mns flies carry a point mutation in a conserved domain of the Shaker gene. Moreover, after crossing out genetic modifiers accumulated over many generations, other Shaker alleles also become short sleepers and fail to complement the mns phenotype. Finally, we show that short-sleeping Shaker flies have a reduced lifespan. Shaker, which encodes a voltage-dependent potassium channel controlling membrane repolarization and transmitter release, may thus regulate sleep need or efficiency.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Behavior, Animal / physiology
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology
  • Conserved Sequence
  • Crosses, Genetic
  • Darkness
  • Drosophila Proteins
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Female
  • Genes, Recessive / genetics
  • Genetic Complementation Test
  • Homeostasis
  • Humans
  • Light
  • Longevity / genetics
  • Longevity / physiology
  • Male
  • Mammals / physiology
  • Molecular Sequence Data
  • Motor Activity / physiology
  • Phenotype
  • Point Mutation / genetics*
  • Potassium Channels / chemistry
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Protein Structure, Tertiary
  • Shaker Superfamily of Potassium Channels
  • Sleep / genetics
  • Sleep / physiology
  • Sleep Deprivation / genetics*
  • Sleep Deprivation / physiopathology*
  • Time Factors
  • X Chromosome / genetics

Substances

  • Drosophila Proteins
  • Potassium Channels
  • Sh protein, Drosophila
  • Shaker Superfamily of Potassium Channels