Evidence map›Paper›PMID 24613312›Full record

ArticleCurrent biology : CB2014

SLEEPLESS is a bifunctional regulator of excitability and cholinergic synaptic transmission.

Meilin Wu, James E Robinson, William J Joiner

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 87 citations in OpenAlex.

  1. Active zone plasticity couples sleep need to presynaptic hypophosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  2. Article
  3. Inferring the genetic basis of sleep states inbioRxiv : the preprint server for biology · 2026
    Article
  4. Sleep regulation inFrontiers in neuroscience · 2026
    Review
  5. 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 · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. 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 · 2023
    Article
  12. ACh Transfers: Homeostatic Plasticity of Cholinergic Synapses.Cellular and molecular neurobiology · 2023
    Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. 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 · 2021
    Article
  18. Review
  19. Layered roles ofeLife · 2020
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Meilin WuDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093-0636, USA.
James E RobinsonDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093-0636, USA; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093-0636, USA.
William J JoinerDepartment of Pharmacology, University of California, San Diego, La Jolla, CA 92093-0636, USA; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA 92093-0636, USA; Neurosciences Graduate Program, University of California, San Diego, La Jolla, CA 92093-0636, USA; Center for Chronobiology, University of California, San Diego, La Jolla, CA 92093-0636, USA. Electronic address: wjoiner@ucsd.edu.
University of California San Diego · US

Funding

GRADUATE TRAINING IN CELLULAR &MOLECULAR PHARMACOLOGYT32GM007752 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BROWN, JOAN HELLER, HANDEL, TRACY M · 1985 to 2023
$13.5M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Molecular and anatomical basis of sleep regulation by SLEEPLESSR01NS072431 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI JOINER, WILLIAM J · 2011 to 2015
$1.7M
NIGMS NIH HHS T32 GM007752NINDS NIH HHS NS072431NINDS NIH HHS P30 NS047101NINDS NIH HHS R01 NS072431
6 · The paper itself

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.

Indexed as

AnimalsCholinergic NeuronsDrosophila melanogasterDrosophila ProteinsGene Knockdown TechniquesMembrane ProteinsMushroom BodiesReceptors, NicotinicShaker Superfamily of Potassium ChannelsSleepSynaptic TransmissionWakefulnessDrosophila ProteinsMembrane ProteinsQvr protein, DrosophilaReceptors, NicotinicShaker Superfamily of Potassium Channels

Identifiers

PMID24613312
PMCPMC4059605
OpenAlexW1985194591

What OpenQuestion holds

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Registered trials

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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.