Cryptochrome Antagonizes Synchronization of Drosophila’s Circadian Clock to Temperature Cycles

Gentile, Carla; Sehadová, Hana; Simoni, Alekos; Chen, Chenghao; Stanewsky, Ralf

doi:10.1016/j.cub.2012.12.023

Cited by 50 publications

(98 citation statements)

References 51 publications

(96 reference statements)

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“…However, experiments performed in our own laboratory (Fig. S3) have failed to find this effect, and subsequent work by other groups has cast doubt on the role of cryptochrome in circadian temperature entrainment (57,58). New data from the laboratory of Patrick Emery (39) suggest that calcium signaling is essential for circadian temperature responses and that the above-mentioned neural pathways converge by calciumdependent degradation of TIM.…”

Section: Resultsmentioning

confidence: 91%

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: Resultsmentioning

confidence: 91%

Temperature compensation and temperature sensation in the circadian clock

Kidd

Young

Siggia

2015

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

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“…Mounted brains were scanned using a Leica TCS SP5 confocal microscope. Quantification of TIM signals was performed as in 38 with minor modifications: Pixel intensity of stained neurons and background staining in each neuronal group was measured using Image J. Background signal was determined by taking the average signal of two surrounding fields of each neuronal group and was subtracted from the neuronal signal.…”

Section: Immunostaining and Quantificationmentioning

confidence: 99%

“…Briefly, the activity from the last two days of each TC was plotted in Excel in 30 min bins and an 'Entrainment Index' (EI = ratio of activity occurring during the 6 h window covering the main activity peak of the positive controls over the activity during the entire warm phase) was calculated. To distinguish the clock-controlled behavioural peaks from temperature response peaks, a simple smoothing filter was applied for the four activity bins during the 2 h following each temperature transition 38 . The filtered data was used for calculation, whereas the raw activity data is plotted in the histograms.…”

Section: Behavioural Analysismentioning

confidence: 99%

“…Plotting of behavioural activity and period calculations were performed using a signal-processing tool-box 40 implemented in Matlab (MathWorks). In order to quantify behaviour during temperature cycles, an updated Histogram version based on Excel (Office, Microsoft) was applied 38 . Briefly, the activity from the last two days of each TC was plotted in Excel in 30 min bins and an 'Entrainment Index' (EI = ratio of activity occurring during the 6 h window covering the main activity peak of the positive controls over the activity during the entire warm phase) was calculated.…”

Section: Behavioural Analysismentioning

confidence: 99%

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Drosophila Ionotropic Receptor 25a mediates circadian clock resetting by temperature

Chen

Buhl

et al. 2015

Nature

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161

176

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Summary:Circadian clocks are endogenous timers adjusting behaviour and physiology with the solar day 1 .Synchronized circadian clocks improve fitness 2 and are crucial for our physical and mental wellbeing 3 . Visual and non-visual photoreceptors are responsible for synchronizing circadian clocks to light 4,5 , but clock-resetting is also achieved by alternating day and night temperatures with only 2°-4°C difference [6][7][8] . This temperature sensitivity is remarkable considering that the circadian clock period (~24 h) is largely independent of surrounding ambient temperatures 1,8 .Here we show that Drosophila Ionotropic Receptor 25a (IR25a) is required for behavioural synchronization to low-amplitude temperature cycles. This channel is expressed in sensory neurons of internal stretch receptors previously implicated in temperature synchronization of the circadian clock 9 . IR25a is required for temperature-synchronized clock protein oscillations in subsets of central clock neurons. Extracellular leg nerve recordings reveal temperature -and IR25a-dependent sensory responses, and IR25a mis-expression confers temperature-dependent firing of heterologous neurons. We propose that IR25a is part of an input pathway to the circadian clock that detects small temperature differences. This pathway operates in the absence of known 'hot' and 'cold' sensors in the Drosophila antenna 10,11 , revealing the existence of novel periphery-to-brain temperature signalling channels. Main Text:In Drosophila, daily activity rhythms are controlled by a network of ~150 clock neurons expressing the clock genes period (per) and timeless (tim). These encode repressor proteins that 3 negatively feedback on their own promoters resulting in 24 h oscillations of clock molecules.Temperature cycles (TC) synchronise molecular clocks present in peripheral appendages in a tissue-autonomous manner 9,12 , while synchronization of clock neurons in the brain largely depends on peripheral temperature receptors located in the chordotonal organs (ChO) and the ChO-expressed gene nocte 9,12,13 .To discover novel factors involved in temperature entrainment, we identified NOCTEinteracting proteins by co-immunoprecipitation and mass-spectrometry (Extended Data Tab. 1) 14 . We focused on IR25a, a member of a divergent subfamily of ionotropic glutamate receptors and verified the interaction by co-immunoprecipitation after overexpressing IR25a and NOCTE in all clock cells using tim-gal4 (Extended Data Fig. 1a). IR25a is expressed in different populations of sensory neurons, including those in the antenna and labellum [15][16][17] . In the olfactory system IR25a acts as a co-receptor with different odour-sensing IRs 15 .To investigate if IR25a is co-expressed with nocte in ChO we analysed IR25a expression in femur and antennal ChO using an IR25a-gal4 line 15 (Extended Data Fig. 2a). IR25a-gal4 driven mCD8-GFP labelled subsets of ChO neurons in the femur, overlapping substantially with nompC-QF driven QUAS-Tomato signals (Fig. 1 a-c). nompC-QF is expressed in larv...

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“…Temperature-sensitive transient receptor potential (TRP) channels are activated at defined temperature values [13,14]. Because temperature entrainment in Drosophila can be achieved with TCs covering their whole physiological temperature range (15-308C), it is possible that different TRP channels are involved in temperature entrainment at different temperature ranges [10,15,16]. The TRP channel encoded by the pyrexia ( pyx) gene is directly activated by temperatures above 388C and protects flies from high temperature stress [17].…”

Section: Introductionmentioning

confidence: 99%

The Pyrexia transient receptor potential channel mediates circadian clock synchronization to low temperature cycles in Drosophila melanogaster

et al. 2013

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Circadian clocks are endogenous approximately 24 h oscillators that temporally regulate many physiological and behavioural processes. In order to be beneficial for the organism, these clocks must be synchronized with the environmental cycles on a daily basis. Both light : dark and the concomitant daily temperature cycles (TCs) function as Zeitgeber ('time giver') and efficiently entrain circadian clocks. The temperature receptors mediating this synchronization have not been identified. Transient receptor potential (TRP) channels function as thermo-receptors in animals, and here we show that the Pyrexia (Pyx) TRP channel mediates temperature synchronization in Drosophila melanogaster. Pyx is expressed in peripheral sensory organs (chordotonal organs), which previously have been implicated in temperature synchronization. Flies deficient for Pyx function fail to synchronize their behaviour to TCs in the lower range (16 -208C), and this deficit can be partially rescued by introducing a wild-type copy of the pyx gene. Synchronization to higher TCs is not affected, demonstrating a specific role for Pyx at lower temperatures. In addition, pyx mutants speed up their clock after being exposed to TCs. Our results identify the first TRP channel involved in temperature synchronization of circadian clocks.

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Cryptochrome Antagonizes Synchronization of Drosophila’s Circadian Clock to Temperature Cycles

Cited by 50 publications

References 51 publications

Temperature compensation and temperature sensation in the circadian clock

Temperature compensation and temperature sensation in the circadian clock

Drosophila Ionotropic Receptor 25a mediates circadian clock resetting by temperature

The Pyrexia transient receptor potential channel mediates circadian clock synchronization to low temperature cycles in Drosophila melanogaster

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