CRY, a Drosophila Clock and Light-Regulated Cryptochrome, Is a Major Contributor to Circadian Rhythm Resetting and Photosensitivity

Emery, Patrick; So, W. Venus; Kaneko, Maki; Hall, Jeffrey C.; Rosbash, Michael

doi:10.1016/s0092-8674(00)81637-2

Cited by 818 publications

(697 citation statements)

References 84 publications

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“…In contrast, repression of splicing in the absence of light requires the circadian clock plus CRY. It seems somewhat counterintuitive that CRY, which is activated by light (5,6,23), plays a more prominent role in repressing splicing at night than it does during the day (Fig. 1E).…”

Section: Resultsmentioning

confidence: 95%

Seasonal behavior in Drosophila melanogaster requires the photoreceptors, the circadian clock, and phospholipase C

Collins

Rosato

Kyriacou

2004

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

118

120

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Drosophila melanogaster locomotor activity responds to different seasonal conditions by thermosensitive regulation of splicing of a 3 intron in the period mRNA transcript. Here we demonstrate that the control of locomotor patterns by this mechanism is primarily light-dependent at low temperatures. At warmer temperatures, when it is vitally important for the fly to avoid midday desiccation, more stringent regulation of splicing is observed, requiring the light input received through the visual system during the day and the circadian clock at night. During the course of this study, we observed that a mutation in the no-receptor-potential-A P41 (norpA P41 ) gene, which encodes phospholipase-C, generated an extremely high level of 3 splicing. This cannot be explained simply by the mutation's effect on the visual pathway and suggests that norpA P41 is directly involved in thermosensitivity.period gene ͉ splicing ͉ locomotor ͉ entrainment ͉ norpA T he period (per) gene in Drosophila melanogaster plays a central role in the circadian clock, acting as a negative regulator of its own transcription (reviewed in ref. 1). A number of other positive and negative transcriptional regulators are interwoven with PER to generate the circadian cycles observed in behavior, including TIMELESS (TIM) and the basic helix-loop-helix transcription factors dCLOCK and CYCLE. In addition, kinases such as DOUBLETIME regulate PER at the protein level, thereby contributing to the timing mechanism (1).Under light͞dark cycles (LD) 12:12, D. melanogaster behavior is bimodal, with a small morning locomotor activity peak at ''lights on'' [Zeitgeber time (ZT)0] and a larger evening activity peak around ''lights off'' (ZT12). Two classic per mutations, per s and per L , alter the free-running period, and under a 24-h Zeitgeber either advance (per s ) or delay into the night phase (per L ) the evening peak, while leaving morning locomotor activity largely unaffected (2). Thus per function is particularly relevant for this latter phase of locomotor behavior, and the importance of this response has been underscored by studies in which elevated temperatures delay the evening peak under LD cycles and cooler temperatures advance it (2-4). This is clearly an adaptive response in that under hot desiccating conditions, the locomotor activity of the fly moves toward the cooler later parts of the day, generating an apparent midday ''siesta'' (4).Temperature changes regulate the splicing of an intron within the 3Ј UTR of per, which then determines the position of the evening locomotor activity peak (4). It might be predicted that the regulation of this event would be tightly controlled, particularly at high temperatures when inappropriate locomotor behavior could prove fatal. We therefore examined the levels of per mRNA splicing in a number of different mutant backgrounds that either eliminate clock function (per 01 and tim 01 ) or impair light input [cry b , gl 60j , and no-receptor-potential-A P41 (norpA P41 )], and combinations thereof.The cry b mutation is c...

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Section: Resultsmentioning

confidence: 95%

Seasonal behavior in Drosophila melanogaster requires the photoreceptors, the circadian clock, and phospholipase C

Collins

Rosato

Kyriacou

2004

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

118

120

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“…Although not definitive, these results support earlier claims that the photoreceptors may directly (or indirectly) synapse with the l-LN v s (40). As stated above, these molecular and proposed functional differences between s-and l-LN v s may also contribute to explaining the loss of light responsiveness in cry b mutant flies, which are blind to constant light and brief light pulses, despite retaining light input from the canonical visual transduction pathway (7,11,41,42). Thus CRYPTOCHROME, aside from being a photoreceptor in its own right, also appears to control a gateway for rhodopsin-mediated light input into the clock.…”

Section: Discussionmentioning

confidence: 91%

Disruption of Cryptochrome partially restores circadian rhythmicity to the arrhythmic period mutant of Drosophila

Collins

Dissel

Gaten

et al. 2005

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

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The Drosophila melanogaster circadian clock is generated by interlocked feedback loops, and null mutations in core genes such as period and timeless generate behavioral arrhythmicity in constant darkness. In light-dark cycles, the elevation in locomotor activity that usually anticipates the light on or off signals is severely compromised in these mutants. Light transduction pathways mediated by the rhodopsins and the dedicated circadian blue light photoreceptor cryptochrome are also critical in providing the circadian clock with entraining light signals from the environment. The cry b mutation reduces the light sensitivity of the fly's clock, yet locomotor activity rhythms in constant darkness or light-dark cycles are relatively normal, because the rhodopsins compensate for the lack of cryptochrome function. Remarkably, when we combined a period-null mutation with cry b , circadian rhythmicity in locomotor behavior in light-dark cycles, as measured by a number of different criteria, was restored. This effect was significantly reduced in timeless-null mutant backgrounds. Circadian rhythmicity in constant darkness was not restored, and TIM protein did not exhibit oscillations in level or localize to the nuclei of brain neurons known to be essential for circadian locomotor activity. Therefore, we have uncovered residual rhythmicity in the absence of period gene function that may be mediated by a previously undescribed period-independent role for timeless in the Drosophila circadian pacemaker. Although we do not yet have a molecular correlate for these apparently iconoclastic observations, we provide a systems explanation for these results based on differential sensitivities of subsets of circadian pacemaker neurons to light.anticipation ͉ phase shift ͉ oscillator ͉ hourglass ͉ timeless T he PERIOD (PER) and TIMELESS (TIM) proteins are core components of the negative feedback loop that drives circadian oscillations in Drosophila. TIM stabilizes PER, and the PER and TIM proteins cooperate in nuclear entry and retention in key pacemaker cells at night (1). TIM degrades rapidly in response to light, releasing PER to repress per and tim transcription (1). D. melanogaster individuals carrying the null mutation per 01 display arrhythmic locomotor activity under constant darkness (DD), whereas in light-dark (LD) cycles, their locomotor activity is elevated under illumination and reduced in darkness, reflecting the ''masking'' effect of light (2, 3). Another mutation in the gene encoding the blue-light photoreceptor cryptochrome, cry b , gives attenuated light responses in a circadian context (4-7), but normal circadian locomotor behavior in 24-h LD cycles. As part of another study of seasonal behavioral responses to temperature and light effected via changes in per 3Ј splicing, we generated a per 01 ; cry b double mutant (8). We noted that a modest cycle in wild-type per 3Ј splicing in LD cycles at 29°C was exaggerated in per 01 and cry b mutants, yet in the double mutant, the amplitude of the splicing reverted back to ap...

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“…Here we demonstrate the utility of this vector with two different enhancer fragments. Others have also used this vector successfully (Emery et al, 1998;Park et al, 2000;Takaesu et al, 2002).…”

mentioning

confidence: 99%

PPTGAL, a convenient Gal4 P‐element vector for testing expression of enhancer fragments in drosophila

Sharma

Cheung

Larsen

et al. 2002

Genesis

117

109

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CRY, a Drosophila Clock and Light-Regulated Cryptochrome, Is a Major Contributor to Circadian Rhythm Resetting and Photosensitivity

Cited by 818 publications

References 84 publications

Seasonal behavior in Drosophila melanogaster requires the photoreceptors, the circadian clock, and phospholipase C

Seasonal behavior in Drosophila melanogaster requires the photoreceptors, the circadian clock, and phospholipase C

Disruption of Cryptochrome partially restores circadian rhythmicity to the arrhythmic period mutant of Drosophila

PPTGAL, a convenient Gal4 P‐element vector for testing expression of enhancer fragments in drosophila

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