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      Identification of SLEEPLESS, a sleep-promoting factor.

      Science (New York, N.Y.)

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

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          Abstract

          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.

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          Author and article information

          Journal
          18635795
          2771549
          10.1126/science.1155942

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