title: Identification of SLEEPLESS, a sleep-promoting factor.
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.
authors.affiliation: Howard Hughes Medical Institute, Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Koh
authors.forename: William J
authors.initials: WJ
authors.lastname: Joiner
authors.forename: Mark N
authors.initials: MN
authors.lastname: Wu
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Yue
authors.forename: Corinne J
authors.initials: CJ
authors.lastname: Smith
authors.forename: Amita
authors.initials: A
authors.lastname: Sehgal
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004251:DNA Transposable Elements; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D005260:Female; D017344:Genes, Insect; D017261:Glycosylphosphatidylinositols; D006706:Homeostasis; D008136:Longevity; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D023421:Models, Animal; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D051637:Shaker Superfamily of Potassium Channels / Q000502:physiology; D015398:Signal Transduction; D012890:Sleep / Q000235:genetics / Q000502:physiology; D012892:Sleep Deprivation; D019076:Transgenes
chemical_list: D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; C530371:Qvr protein, Drosophila; C496929:Sh protein, Drosophila; D051637:Shaker Superfamily of Potassium Channels