insomniac and Cullin-3 Regulate Sleep and Wakefulness in Drosophila

Stavropoulos, Nicholas; Young, Michael W.

doi:10.1016/j.neuron.2011.12.003

Cited by 150 publications

(260 citation statements)

References 69 publications

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“…Phase shifts were computed as before, by comparing to a control group kept at 25°C. Sleep measurements were made in DD using flies entrained in the same manner and judging sleep as beginning after a 5-min period of inactivity (81,82).…”

Section: Methodsmentioning

confidence: 99%

Temperature compensation and temperature sensation in the circadian clock

Kidd

Young

Siggia

2015

Proc. Natl. Acad. Sci. U.S.A.

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All known circadian clocks have an endogenous period that is remarkably insensitive to temperature, a property known as temperature compensation, while at the same time being readily entrained by a diurnal temperature oscillation. Although temperature compensation and entrainment are defining features of circadian clocks, their mechanisms remain poorly understood. Most models presume that multiple steps in the circadian cycle are temperature-dependent, thus facilitating temperature entrainment, but then insist that the effect of changes around the cycle sums to zero to enforce temperature compensation. An alternative theory proposes that the circadian oscillator evolved from an adaptive temperature sensor: a gene circuit that responds only to temperature changes. This theory implies that temperature changes should linearly rescale the amplitudes of clock component oscillations but leave phase relationships and shapes unchanged. We show using timeless luciferase reporter measurements and Western blots against TIMELESS protein that this prediction is satisfied by the Drosophila circadian clock. We also review evidence for pathways that couple temperature to the circadian clock, and show previously unidentified evidence for coupling between the Drosophila clock and the heat-shock pathway.circadian clock | temperature compensation | mathematical models C ircadian rhythms are daily oscillations in gene expression and protein concentration that regulate sleep (1, 2), metabolism (3,4), and a host of other biological processes (5-8). Circadian oscillations are known to be present in nearly all animals and plants, as well as some fungi and bacteria (9). In all organisms in which circadian oscillations have been observed, circadian oscillations satisfy three defining properties (10). First, circadian oscillations are self-sustained and spontaneously maintain a period of about 24 h. Second, the circadian rhythm is sensitive to light and temperature and can be synchronized to external oscillations in the quantity of either. Third, the period of the circadian oscillation is "temperature-compensated"; that is, the endogenous period of the oscillation is relatively insensitive to temperature.The genetic basis of circadian clocks has been elucidated in considerable detail over the past two decades, particularly in the fruitfly Drosophila melanogaster, the mouse Mus musculus, and the bread mold Neurospora crassa (11). In Drosophila, a self-sustained circadian oscillation in neurons is generated when a pair of proteins, PERIOD (PER) and TIMELESS (TIM), dimerize and, after some delay, translocate into the nucleus, where the proteins repress their own transcription by inactivating a transcription factor dimer composed of the proteins CLOCK and CYCLE. Light sensitivity is mediated by the blue light photoreceptor CRYPTOCHROME (CRY), which upon activation binds TIMELESS and promotes TIMELESS degradation. A remarkably similar mechanism underlies circadian clocks in mouse and Neurospora. The circadian clock of cyanobacteria has also bee...

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Section: Methodsmentioning

confidence: 99%

Temperature compensation and temperature sensation in the circadian clock

Kidd

Young

Siggia

2015

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition, elevated dopamine can also reduce rebound sleep, suggesting a contribution to sleep homeostasis (Kume et al 2005). The E3 ubiquitin ligase Cullin-3 (Cul3) and its substrate adaptor, inc, have potent roles in both baseline and recovery sleep (Stavropoulos and Young 2011;Pfeiffenberger and Allada 2012). These effects depend on DA but do not occur in DA neurons (Pfeiffenberger and Allada 2012).…”

Section: Acetylcholinementioning

confidence: 99%

Molecular Mechanisms of Sleep Homeostasis in Flies and Mammals

Allada¹,

Cirelli

Sehgal

2017

Cold Spring Harb Perspect Biol

133

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“…Partitioning of heritability across tissue types 25,26 showed enrichment in the central nervous system, adrenal/pancreas tissue lineages and skeletal muscle (p<10 -5 ) (Supplementary Table 17 [29][30][31][32] . Furthermore, the restless legs syndrome gene BTBD9 has been implicated as a substrate adaptor for the Cullin-3 class of E3 ubiquitin ligases 33 .…”

mentioning

confidence: 99%

Biological and clinical insights from genetics of insomnia symptoms

Lane

Jones

Dashti

et al. 2018

Preprint

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Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes, but underlying pathophysiological processes and causal relationships with disease are poorly understood. Here we identify 57 loci for self-reported insomnia symptoms in the UK Biobank (n=453,379) and confirm their impact on self-reported insomnia symptoms in the HUNT study (n=14,923 cases, 47,610 controls), physician diagnosed insomnia in Partners Biobank (n=2,217 cases, 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n=83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis, phototransduction and muscle development pathways and of genes expressed in multiple brain regions, skeletal muscle and adrenal gland. Evidence of shared genetic factors is found between frequent insomnia symptoms and restless legs syndrome, aging, cardio-metabolic, behavioral, psychiatric and reproductive traits. Evidence is found for a possible causal link between insomnia symptoms and coronary heart disease, depressive symptoms and subjective well-being.

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insomniac and Cullin-3 Regulate Sleep and Wakefulness in Drosophila

Cited by 150 publications

References 69 publications

Temperature compensation and temperature sensation in the circadian clock

Temperature compensation and temperature sensation in the circadian clock

Molecular Mechanisms of Sleep Homeostasis in Flies and Mammals

Biological and clinical insights from genetics of insomnia symptoms

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