ArticleFly
An emerging role for Cullin-3 mediated ubiquitination in sleep and circadian rhythm: insights from Drosophila.
Article in Fly. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Sleep regulation inFrontiers in neuroscience · 2026Review
- Small Peptides Isolated from Enzymatic Hydrolyzate ofFoods (Basel, Switzerland) · 2023Article
- Ubiquitin proteasome system in circadian rhythm and sleep homeostasis: Lessons from Drosophila.Genes to cells : devoted to molecular & cellular mechanisms · 2022Review
- Integrative Proteome and Ubiquitinome Analyses Reveal the Substrates of BTBD9 and Its Underlying Mechanism in Sleep Regulation.ACS omega · 2022Article
- Rotigotine suppresses sleep-related muscle activity augmented by injection of dialysis patients' sera in a mouse model of restless legs syndrome.Scientific reports · 2019Article
- Iron Deficiency Reduces Synapse Formation in the Drosophila Clock Circuit.Biological trace element research · 2019Article
- Biological and clinical insights from genetics of insomnia symptoms.Nature genetics · 2019Article
- Impact of Autophagy and Aging on Iron Load and Ferritin inFrontiers in cell and developmental biology · 2019Article
- Thirty loci identified for heart rate response to exercise and recovery implicate autonomic nervous system.Nature communications · 2018Article
- Article
- Iron Sulfur and Molybdenum Cofactor Enzymes Regulate theFrontiers in physiology · 2018Article
- Animal models of RLS phenotypes.Sleep medicine · 2017Review
- Improved statistical methods enable greater sensitivity in rhythm detection for genome-wide data.PLoS computational biology · 2015Article
- Conserved metallomics in two insect families evolving separately for a hundred million years.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2014Article
- Dopamine dynamics and signaling in Drosophila: an overview of genes, drugs and behavioral paradigms.Experimental animals · 2014Review
- Identification and Expression Profiling of the BTB Domain-Containing Protein Gene Family in the Silkworm, Bombyx mori.International journal of genomics · 2014Article
- Iron absorption in Drosophila melanogaster.Nutrients · 2013Review
- A recessive X-linked mutation causes a threefold reduction of total body zinc accumulation in Drosophila melanogaster laboratory strains.FEBS open bio · 2013Article
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Authors and funding
4 authors at 4 institutions in 4 countries.
Funding
Abstract
Although the neurophysiological correlates of sleep have been thoroughly described, genetic mechanisms that control sleep architecture, long surmised from ethological studies, family histories and clinical observations, have only been investigated during the past decade. Key contributions to the molecular understanding of sleep have come from studies in Drosophila, benefitting from a strong history of circadian rhythm research. For instance, a number of recent papers have highlighted the role of the E3 ubiquitin ligase Cullin-3 in the regulation of circadian rhythm and sleep. We propose that different Cullin-3 substrate adaptors may affect specific molecular pathways and diverse aspects of circadian rhythm and sleep. We have previously shown that mutations in BTBD9, a risk factor for Restless Legs Syndrome (RLS) encoding a Cullin-3 substrate adaptor, lead to reduced dopamine, increased locomotion and sleep fragmentation. Here, we propose that Cullin-3 acts together with BTBD9 to limit the accumulation of iron regulatory proteins in conditions of iron deficiency. Our model is consistent with clinical observations implicating iron homeostasis in the pathophysiology of RLS and predicts that lack of BTBD9 leads to misregulation of cellular iron storage, inactivating the critical biosynthetic enzyme Tyrosine Hydroxylase in dopaminergic neurons, with consequent phenotypic effects on sleep.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.