insomniac and Cullin-3 Regulate Sleep and Wakefulness in Drosophila

• Published in: Neuron (Cambridge, Mass.) Mass.), 2011-12, Vol.72 (6), p.964-976
• Main Authors: Stavropoulos, Nicholas, Young, Michael W.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Animals, Genetically Modified; Base Sequence; Behavior; Circadian Clocks - genetics; Circadian rhythm; Cloning; Conserved Sequence - genetics; Cullin Proteins - genetics; Cullin Proteins - physiology; Drosophila; Drosophila melanogaster - genetics; Drosophila Proteins - antagonists & inhibitors; Drosophila Proteins - genetics; Drosophila Proteins - physiology; Female; Insects; Male; Mammals; Molecular Sequence Data; Monitoring systems; Mutation; Phenotype; Proteins; RNA, Small Interfering - genetics; Sleep - genetics; Ubiquitin-Protein Ligases - antagonists & inhibitors; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - physiology; Wakefulness - genetics
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2011.12.003

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. ► Mutations in insomniac reduce sleep duration and consolidation in Drosophila ► insomniac regulates sleep by a mechanism distinct from the circadian clock ► insomniac encodes a putative Cul3 adaptor and is highly conserved in vertebrates ► insomniac and Cul3 function within neurons to control sleep