Identification of SLEEPLESS, a sleep-promoting factor
Open accessAbstract
Sleep is an essential process conserved from flies to humans. The importance of sleep is underscored by its tight homeostatic control. Through a forward genetic screen, we identified a gene, sleepless, required for sleep in Drosophila. The sleepless gene encodes a brain-enriched, glycosylphosphatidylinositol-anchored protein. Loss of SLEEPLESS protein caused an extreme (>80%) reduction in sleep; a moderate reduction in SLEEPLESS had minimal effects on baseline sleep but markedly reduced the amount of recovery sleep after sleep deprivation. Genetic and molecular analyses revealed that quiver, a mutation that impairs Shaker-dependent potassium current, is an allele of sleepless. Consistent with this finding, Shaker protein levels were reduced in sleepless mutants. We propose that SLEEPLESS is a signaling molecule that connects sleep drive to lowered membrane excitability.
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Elevated levels of SSS are required for sleep rebound in order to overcome the circadian-based morning waking drive.
“Elevated levels of SSS are required for sleep rebound in order to overcome the circadian-based morning waking drive.”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Koh et al., 2008
A novel gene, sleepless (sss), acts as a signaling molecule necessary for maintenance of baseline and rebound sleep in Drosophila.
“Furthermore, a large scale, unbiased genetic screening identified a novel gene, sleepless (sss), that acts as a signaling molecule necessary for maintenance of baseline and rebound sleep in Drosophila (Koh et al., 2008).”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Koh et al., 2008
In Drosophila, the regulation of sleep involves an interaction of the circadian system that controls the timing of sleep with a homeostatic system that regulates the need for sleep.
“In Drosophila the regulation of sleep involves an interaction of the circadian system that controls the timing of sleep with a homeostatic system that regulates the need for sleep (Koh et al., 2008).”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Koh et al., 2008
Loss of the SLEEPLESS protein reduced sleep by more than 80%, whereas reduced SLEEPLESS protein had little effect on baseline sleep but impaired rebound sleep.
“Loss of the SLEEPLESS protein reduced sleep by >80%, whereas reduced SLEEPLESS protein had little effect on baseline sleep, but impaired rebound sleep.”
From Biological rhythms, higher brain function, and behavior: Gaps, opportunities, and challenges (2009) · cites this paper as Koh et al., 2008
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“Similarly, reduced sleep and life span have been reported for flies with a loss of the gene Sleepless (SSS) which codes for glycosylphosphatidylinositol-anchored protein with unknown function, with the effects of this mutation possibly in part also mediated by Shaker channels (202, 272, 653, 1306, 1337).”
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Self-citation
- Authors
- Koh, K., Joiner, W. J., Wu, M. N., Yue, Z., Smith, C. J., & Sehgal, A.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Koh, Kyunghee
- Joiner, William J.
- Wu, Mark N.
- Sehgal, Amita
- Venue
- Science
- Published
- 2008-07-18
- Volume
- 321
- Issue
- 5887
- Pages
- 372-376
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC2771549
- OpenAlex
- W1990296960
- Cited by
- 347
- References
- 38
- Citations by year
- 2026: 20 · 2025: 27 · 2024: 17 · 2023: 18 · 2022: 16 · 2021: 11 · 2020: 20 · 2019: 18 · 2018: 20 · 2017: 22 · 2016: 17 · 2015: 23 · 2014: 20 · 2013: 22 · 2012: 16
- FWCI
- 10.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute on Aging (P01AG017628, AG017628)
- National Institute of Neurological Disorders and Stroke (R01NS072431)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- sleep, sleep homeostasis, GPI-anchored proteins, Shaker potassium channel, quiver mutation, membrane excitability, sleep drive, Drosophila
- MeSH terms
- Amino Acid Sequence, Animals, Behavior, Animal, Brain, Cell Membrane, DNA Transposable Elements, Drosophila melanogaster, Female, Homeostasis, Longevity, Male, Membrane Proteins, Molecular Sequence Data, Mutation, Phenotype, Sleep, Sleep Deprivation, Signal Transduction, Glycosylphosphatidylinositols, Genes, Insect, Transgenes, Models, Animal, Drosophila Proteins, Animals, Genetically Modified, Shaker Superfamily of Potassium Channels
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