ArticlePLoS genetics2012
Cul3 and the BTB adaptor insomniac are key regulators of sleep homeostasis and a dopamine arousal pathway in Drosophila.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 119 citations in OpenAlex.
- Inferring the genetic basis of sleep states inbioRxiv : the preprint server for biology · 2026Article
- The use ofFrontiers in cell and developmental biology · 2026Review
- Sleep regulation inFrontiers in neuroscience · 2026Review
- KCTD Family: Emerging Regulators of GPCR Biased Signaling.Handbook of experimental pharmacology · 2026Review
- 25 years ofFly · 2025Review
- Targeted single cell expression profiling identifies integrators of sleep and metabolic state.G3 (Bethesda, Md.) · 2025Article
- Enhanced memory despite severe sleep loss in Drosophila insomniac mutants.PLoS biology · 2025Article
- The Cul3 ubiquitin ligase engages Insomniac as an adaptor to impact sleep and synaptic homeostasis.PLoS genetics · 2025Article
- Large-language models facilitate discovery of the molecular signatures regulating sleep and activity.Nature communications · 2024Article
- Sleep deprivation drives brain-wide changes in cholinergic presynapse abundance inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Comprehensive Analysis of the Structural Recognition between KCTD Proteins and Cullin 3.International journal of molecular sciences · 2024Article
- Neuronal knockdown of Cullin3 as a Drosophila model of autism spectrum disorder.Scientific reports · 2024Article
- Structural basis for the ubiquitination of G protein βγ subunits by KCTD5/Cullin3 E3 ligase.Science advances · 2023Article
- A brain-wide form of presynaptic active zone plasticity orchestrates resilience to brain aging in Drosophila.PLoS biology · 2022Article
- TheiScience · 2022Article
- Article
- Ubiquitin proteasome system in circadian rhythm and sleep homeostasis: Lessons from Drosophila.Genes to cells : devoted to molecular & cellular mechanisms · 2022Review
- Synaptic dysfunction connects autism spectrum disorder and sleep disturbances: A perspective from studies in model organisms.Sleep medicine reviews · 2022Review
- The microtubule-associated protein Tau suppresses the axonal distribution of PDF neuropeptide and mitochondria in circadian clock neurons.Human molecular genetics · 2022Article
- Article
4 more citing papers are in PubMed but not listed here.
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2 authors at 1 institution in 1 country.
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Abstract
Sleep is homeostatically regulated, such that sleep drive reflects the duration of prior wakefulness. However, despite the discovery of genes important for sleep, a coherent molecular model for sleep homeostasis has yet to emerge. To better understand the function and regulation of sleep, we employed a reverse-genetics approach in Drosophila. An insertion in the BTB domain protein CG32810/insomniac (inc) exhibited one of the strongest baseline sleep phenotypes thus far observed, a ~10 h sleep reduction. Importantly, this is coupled to a reduced homeostatic response to sleep deprivation, consistent with a disrupted sleep homeostat. Knockdown of the INC-interacting protein, the E3 ubiquitin ligase Cul3, results in reduced sleep duration, consolidation, and homeostasis, suggesting an important role for protein turnover in mediating INC effects. Interestingly, inc and Cul3 expression in post-mitotic neurons during development contributes to their adult sleep functions. Similar to flies with increased dopaminergic signaling, loss of inc and Cul3 result in hyper-arousability to a mechanical stimulus in adult flies. Furthermore, the inc sleep duration phenotype can be rescued by pharmacological inhibition of tyrosine hydroxylase, the rate-limiting enzyme for dopamine biosynthesis. Taken together, these results establish inc and Cul3 as important new players in setting the sleep homeostat and a dopaminergic arousal pathway in Drosophila.
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