title: insomniac and Cullin-3 regulate sleep and wakefulness in Drosophila.
abstract: In a forward genetic screen in Drosophila, we have isolated insomniac, a mutant that severely reduces the duration and consolidation of sleep. Anatomically restricted genetic manipulations indicate that insomniac functions within neurons to regulate sleep. insomniac expression does not oscillate in a circadian manner, and conversely, the circadian clock is intact in insomniac mutants, suggesting that insomniac regulates sleep by pathways distinct from the circadian clock. The protein encoded by insomniac is a member of the BTB/POZ superfamily, which includes many proteins that function as adaptors for the Cullin-3 (Cul3) ubiquitin ligase complex. We show that Insomniac can physically associate with Cul3, and that reduction of Cul3 activity in neurons recapitulates the insomniac phenotype. The extensive evolutionary conservation of insomniac and Cul3 suggests that protein degradation pathways may have a general role in governing the sleep and wakefulness of animals.
authors.affiliation: Laboratory of Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Stavropoulos
authors.forename: Michael W
authors.initials: MW
authors.lastname: Young
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D057906:Circadian Clocks / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D044842:Cullin Proteins / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics; D005260:Female; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D034741:RNA, Small Interfering / Q000235:genetics; D012890:Sleep / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014851:Wakefulness / Q000235:genetics*
chemical_list: C503647:Cul3 protein, Drosophila; D044842:Cullin Proteins; D029721:Drosophila Proteins; C569969:Inc protein, Drosophila; D034741:RNA, Small Interfering; D044767:Ubiquitin-Protein Ligases