A new role for cryptochrome in a Drosophila circadian oscillator

Krishnan, Balaji; Levine, Joel D.; Lynch, Michael; Dowse, Harold B.; Funes, Pablo; Hall, Jeffrey C.; Hardin, Paul E.; Dryer, Stuart E.

doi:10.1038/35077094

Cited by 218 publications

(200 citation statements)

References 25 publications

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“…This result is in contrast to other peripheral tissues, including the antennae, legs, photoreceptor cells, and Malpighian tubules, where CRY plays a role as a core component of the circadian oscillator and the circadian molecular oscillations are absent in cry b or cry 0 flies in DD (9,10,(18)(19)(20)(21). In the photoreceptor cells of the compound eyes, CRY functions as a transcriptional repressor of the CLK-CYCactivated transcription (22).…”

Section: Discussionmentioning

confidence: 97%

“…However, there is a remarkable difference that, in the peripheral oscillator, CRY functions as a core component besides a photoreceptor. In cry b (a cry loss-of-function mutant) and cry 0 (a KO mutant of cry) flies, molecular oscillations of the clock genes and proteins are absent in peripheral tissues (i.e., the compound eyes, antennae, legs, and Malpighian tubules) (10,(18)(19)(20)(21). In the compound eyes, CRY is suggested to act as a repressor of the CLK/CYC transcriptional activity (22).…”

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confidence: 99%

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Peripheral circadian clock for the cuticle deposition rhythm in Drosophila melanogaster

Ito

Goto

Shiga

et al. 2008

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

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Insect endocuticle thickens after adult emergence by daily alternating deposition of two chitin layers with different orientation. Although the cuticle deposition rhythm is known to be controlled by a circadian clock in many insects, the site of the driving clock, the photoreceptor for entrainment, and the oscillatory mechanism remain elusive. Here, we show that the cuticle deposition rhythm is regulated by a peripheral oscillator in the epidermis in Drosophila melanogaster. Free-running and entrainment experiments in vitro reveal that the oscillator for the cuticle deposition rhythm is independent of the central clock in the brain driving the locomotor rhythms. The cuticle deposition rhythm is absent in null and dominant-negative mutants of clock genes (i.e., period, timeless, cycle, and Clock), indicating that this oscillator is composed of the same clock genes as the central clock. Entrainment experiments with monochromatic light-dark cycles and cry b flies reveal that a blue light-absorbing photoreceptor, cryptochrome (CRY), acts as a photoreceptor pigment for the entrainment of the cuticle deposition rhythm. Unlike other peripheral rhythms in D. melanogaster, the cuticle deposition rhythm persisted in cry b and cry OUT mutant flies, indicating that CRY does not play a core role in the rhythm generation in the epidermal oscillator.circadian rhythm ͉ clock genes ͉ cryptochrome ͉ entrainment ͉ epidermal cell C ircadian clocks control daily rhythms at the molecular, physiological, and behavioral levels. Like most organisms, the central circadian oscillator controlling the locomotor activity rhythm in Drosophila is proposed to consist of molecular feedback loops. The feedback loops comprise several core clock genes, such as period (per), timeless (tim), Clock (Clk), and cycle (cyc) (1). These genes encode PER, TIM, CLK, and CYC proteins, respectively, and loss-of-function or dominant-negative mutations in these genes result in loss of normal circadian rhythmicity (2-5). CLK and CYC form a heterodimer to activate transcription of per and tim (2, 4, 6). PER and TIM form another heterodimer, are transferred into the nucleus, and then inactivate the transcriptional activity of the CLK/CYC heterodimer (6). The feedback loops are entrained and reset by the lightinduced degradation of TIM mediated by a photoreceptor pigment, cryptochrome (CRY) (7-10).In addition to the central oscillator, peripheral oscillators exist in many tissues, including the compound eyes, antennae, wings, legs, and Malpighian tubules in adults and the ring gland in pupae (11)(12)(13)(14). These oscillators are self-sustained and directly light-entrainable even in vitro (11-13). In addition, the oscillators are clearly independent of the central circadian oscillator(s) in the brain (15, 16). Previous reports revealed that the peripheral oscillator shares the same genes with the central clock in the brain (12, 17). However, there is a remarkable difference that, in the peripheral oscillator, CRY functions as a core component besides a photorecepto...

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Peripheral circadian clock for the cuticle deposition rhythm in Drosophila melanogaster

Ito

Goto

Shiga

et al. 2008

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

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“…Thirty adult male Canton-S fly wings were dissected and cultured as described 64 under 12 h light/12 h dark (LD) conditions for 3 days. In mRNA half-life measurements actinomycin D was added in ZT3 (10 mg ml À 1 ), wings were transferred into TRI Reagent (SIGMA) at relevant time points and mRNA was extracted.…”

Section: Methodsmentioning

confidence: 99%

Clk post-transcriptional control denoises circadian transcription both temporally and spatially

et al. 2015

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The transcription factor CLOCK (CLK) is essential for the development and maintenance of circadian rhythms in Drosophila. However, little is known about how CLK levels are controlled. Here we show that Clk mRNA is strongly regulated post-transcriptionally through its 3 0 UTR. Flies expressing Clk transgenes without normal 3 0 UTR exhibit variable CLK-driven transcription and circadian behaviour as well as ectopic expression of CLK-target genes in the brain. In these flies, the number of the key circadian neurons differs stochastically between individuals and within the two hemispheres of the same brain. Moreover, flies carrying Clk transgenes with deletions in the binding sites for the miRNA bantam have stochastic number of pacemaker neurons, suggesting that this miRNA mediates the deterministic expression of CLK. Overall our results demonstrate a key role of Clk post-transcriptional control in stabilizing circadian transcription, which is essential for proper development and maintenance of circadian rhythms in Drosophila.

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“…Krishnan et al 1999); these results led to the suggestion that CRY functions as a ''clock protein'' in the periphery (Krishnan et al 2001;cf. Ivanchenko et al 2001;Collins et al 2006).…”

Section: P24mentioning

confidence: 99%

Rhythm Defects Caused by Newly Engineered Null Mutations in Drosophila's cryptochrome Gene

Doleželová¹,

Doležel²,

2007

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Much of the knowledge about cryptochrome function in Drosophila stems from analyzing the cry b mutant. Several features of this variant's light responsiveness imply either that CRY b retains circadianphotoreceptive capacities or that additional CRY-independent light-input routes subserve these processes. Potentially to resolve these issues, we generated cry knock-out mutants (cry 0 's) by gene replacement. They behaved in an anomalously rhythmic manner in constant light (LL). However, cry 0 flies frequently exhibited two separate circadian components in LL, not observed in most previous cry b analyses. Temperature-dependent circadian phenotypes exhibited by cry 0 flies suggest that CRY is involved in core pacemaking. Further locomotor experiments combined cry 0 with an externally blinding mutation (norpA P24 ), which caused the most severe decrements of circadian photoreception observed so far. cry b cultures were shown previously to exhibit either aperiodic or rhythmic eclosion in separate studies. We found cry 0 to eclose in a solidly periodic manner in light:dark cycles or constant darkness. Furthermore, both cry 0 and cry b eclosed rhythmically in LL. These findings indicate that the novel cry 0 type causes more profound defects than does the cry b mutation, implying that CRY b retains residual activity. Because some norpA P24 cry 0 individuals can resynchronize to novel photic regimes, an as-yet undetermined light-input route exists in Drosophila.

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A new role for cryptochrome in a Drosophila circadian oscillator

Cited by 218 publications

References 25 publications

Peripheral circadian clock for the cuticle deposition rhythm in Drosophila melanogaster

Peripheral circadian clock for the cuticle deposition rhythm in Drosophila melanogaster

Clk post-transcriptional control denoises circadian transcription both temporally and spatially

Rhythm Defects Caused by Newly Engineered Null Mutations in Drosophila's cryptochrome Gene

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