title: SLEEPLESS, a Ly-6/neurotoxin family member, regulates the levels, localization and activity of Shaker.
abstract: Sleep is a whole-organism phenomenon accompanied by global changes in neural activity. We previously identified SLEEPLESS (SSS) as a glycosylphosphatidyl inositol-anchored protein required for sleep in Drosophila. Here we found that SSS is critical for regulating the sleep-modulating potassium channel Shaker. SSS and Shaker shared similar expression patterns in the brain and specifically affected each other's expression levels. sleepless (sss) loss-of-function mutants exhibited altered Shaker localization, reduced Shaker current density and slower Shaker current kinetics. Transgenic expression of sss in sss mutants rescued defects in Shaker expression and activity cell-autonomously and suggested that SSS functions in wake-promoting, cholinergic neurons. In heterologous cells, SSS accelerated the kinetics of Shaker currents and was co-immunoprecipitated with Shaker, suggesting that SSS modulates Shaker activity via a direct interaction. SSS is predicted to belong to the Ly-6/neurotoxin superfamily, suggesting a mechanism for regulation of neuronal excitability by endogenous toxin-like molecules.
authors.affiliation: Division of Sleep Medicine, Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Mark N
authors.initials: MN
authors.lastname: Wu
authors.forename: William J
authors.initials: WJ
authors.lastname: Joiner
authors.forename: Terry
authors.initials: T
authors.lastname: Dean
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Yue
authors.forename: Corinne J
authors.initials: CJ
authors.lastname: Smith
authors.forename: Dechun
authors.initials: D
authors.lastname: Chen
authors.forename: Toshinori
authors.initials: T
authors.lastname: Hoshi
authors.forename: Amita
authors.initials: A
authors.lastname: Sehgal
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Koh
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002461:Cell Line, Transformed; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D066298:In Vitro Techniques; D007814:Larva; D008565:Membrane Proteins / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D009469:Neuromuscular Junction / Q000235:genetics / Q000502:physiology; D011984:Sensory Receptor Cells / Q000378:metabolism; D051637:Shaker Superfamily of Potassium Channels / Q000378:metabolism*; D012890:Sleep / Q000235:genetics; D014851:Wakefulness / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; C530371:Qvr protein, Drosophila; C496929:Sh protein, Drosophila; D051637:Shaker Superfamily of Potassium Channels; D049452:Green Fluorescent Proteins