RRC ID 15550
Author Stavropoulos N, Young MW.
Title insomniac and Cullin-3 regulate sleep and wakefulness in Drosophila.
Journal Neuron
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.
Volume 72(6)
Pages 964-76
Published 2011-12-22
DOI 10.1016/j.neuron.2011.12.003
PII S0896-6273(11)01045-2
PMID 22196332
PMC PMC3244879
MeSH Amino Acid Sequence Animals Animals, Genetically Modified Base Sequence Circadian Clocks / genetics Conserved Sequence / genetics Cullin Proteins / genetics Cullin Proteins / physiology* Drosophila Proteins / antagonists & inhibitors Drosophila Proteins / genetics Drosophila Proteins / physiology* Drosophila melanogaster / genetics Female Male Molecular Sequence Data Mutation Phenotype RNA, Small Interfering / genetics Sleep / genetics* Ubiquitin-Protein Ligases / antagonists & inhibitors Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / physiology* Wakefulness / genetics*
IF 14.415
Times Cited 79
WOS Category NEUROSCIENCES
Resource
Drosophila 1512R-3 11861R-2 31829R-2