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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Animals, Genetically Modified
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Behavior, Animal
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Brain / metabolism
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Cell Membrane / metabolism
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DNA Transposable Elements
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Drosophila Proteins / chemistry
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Drosophila Proteins / genetics*
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Drosophila Proteins / physiology*
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Drosophila melanogaster / genetics
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Drosophila melanogaster / physiology*
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Female
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Genes, Insect*
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Glycosylphosphatidylinositols
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Homeostasis
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Longevity
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Male
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Membrane Proteins / chemistry
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Membrane Proteins / genetics*
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Membrane Proteins / physiology*
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Models, Animal*
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Molecular Sequence Data
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Mutation
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Phenotype
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Shaker Superfamily of Potassium Channels / physiology
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Signal Transduction
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Sleep Deprivation
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Sleep* / genetics
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Sleep* / physiology
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Transgenes
Substances
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DNA Transposable Elements
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Drosophila Proteins
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Glycosylphosphatidylinositols
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Membrane Proteins
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Qvr protein, Drosophila
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Sh protein, Drosophila
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Shaker Superfamily of Potassium Channels