ArticleCurrent biology : CB2014
SLEEPLESS is a bifunctional regulator of excitability and cholinergic synaptic transmission.
Article in Current biology : CB, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 87 citations in OpenAlex.
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- Inferring the genetic basis of sleep states inbioRxiv : the preprint server for biology · 2026Article
- Sleep regulation inFrontiers in neuroscience · 2026Review
- Deficiency in transmitter release triggers homeostatic transcriptional changes that increase presynaptic excitability.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Identification of a Tick Midgut Protein Involved inMicroorganisms · 2025Article
- Altered Metabolism during the Dark Period in Drosophila Short Sleep Mutants.Journal of proteome research · 2024Article
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- The zebrafish mutanteLife · 2023Article
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- Control of Synaptic Levels of Nicotinic Acetylcholine Receptor by the Sequestering Subunit Dα5 and Secreted Scaffold Protein Hig.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- ACh Transfers: Homeostatic Plasticity of Cholinergic Synapses.Cellular and molecular neurobiology · 2023Review
- New Three-Finger Protein from StarfishMarine drugs · 2022Article
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- Changes in Locomotor Activity and Oxidative Stress-Related Factors after the Administration of an Amino Acid Mixture by Generation and Age.International journal of molecular sciences · 2021Article
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- Temporal regulation of nicotinic acetylcholine receptor subunits supports central cholinergic synapse development inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Constructing and Tuning Excitatory Cholinergic Synapses: The Multifaceted Functions of Nicotinic Acetylcholine Receptors inFrontiers in cellular neuroscience · 2021Review
- Layered roles ofeLife · 2020Article
- The voltage-gated potassium channel Shaker promotes sleep via thermosensitive GABA transmission.Communications biology · 2020Article
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3 authors at 1 institution in 1 country.
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Abstract
backgroundAlthough sleep is conserved throughout evolution, the molecular basis of its control is still largely a mystery. We previously showed that the quiver/sleepless (qvr/sss) gene encodes a membrane-tethered protein that is required for normal sleep in Drosophila. SLEEPLESS (SSS) protein functions, at least in part, by upregulating the levels and open probability of Shaker (Sh) potassium channels to suppress neuronal excitability and enable sleep. Consistent with this proposed mechanism, loss-of-function mutations in Sh phenocopy qvr/sss-null mutants. However, sleep is more genetically modifiable in Sh than in qvr/sss mutants, suggesting that SSS may regulate additional molecules to influence sleep.
resultsHere we show that SSS also antagonizes nicotinic acetylcholine receptors (nAChRs) to reduce synaptic transmission and promote sleep. Mimicking this antagonism with the nAChR inhibitor mecamylamine or by RNAi knockdown of specific nAChR subunits is sufficient to restore sleep to qvr/sss mutants. Regulation of nAChR activity by SSS occurs posttranscriptionally, since the levels of nAChR mRNAs are unchanged in qvr/sss mutants. Regulation of nAChR activity by SSS may in fact be direct, since SSS forms a stable complex with and antagonizes nAChR function in transfected cells. Intriguingly, lynx1, a mammalian homolog of SSS, can partially restore normal sleep to qvr/sss mutants, and lynx1 can form stable complexes with Shaker-type channels and nAChRs.
conclusionsTogether, our data point to an evolutionarily conserved, bifunctional role for SSS and its homologs in controlling excitability and synaptic transmission in fundamental processes of the nervous system such as sleep.
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