Light-dependent interaction between Drosophila CRY and the clock protein PER mediated by the carboxy terminus of CRY

Rosato, Ezio; Codd, Veryan; Mazzotta, Gabriella; Piccin, Alberto; Zordan, Mauro Agostino; Costa, Rodolfo; Kyriacou, Charalambos P.

doi:10.1016/s0960-9822(01)00259-7

Cited by 134 publications

(139 citation statements)

References 24 publications

(14 reference statements)

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“…Fig. 6 reveals that WT and norpA P41 show similar profiles (Table 1, lines [24][25][26], with an earlier per mRNA peak and higher overall level of per at the lower temperature. In contrast, there is no cycle in gl 60j at either temperature, and levels of per are significantly different from WT and norpA P41 (Table 1, line 27).…”

Section: Resultsmentioning

confidence: 68%

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.

117

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: 68%

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.

117

120

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“…The immunoprecipitated materials and whole cell extracts were analyzed by immunoblotting with anti-VP16 (zCRY1a and chimera 17), anti-zCRY3 (chimeras 11, 18, and zCRY3), anti-V5 (zB-MAL3), or anti-FLAG antibodies (zCLOCK1). The abbreviations c 5,11,12,13,14,16,17, and 18 respectively indicate chimeras 5, 11, 12, 13, 14, 16, 17, and 18. localization (Fig. 4C, lanes 7-18).…”

Section: Fig 2 Determination Of the Zcry1a Regions Required For Tramentioning

confidence: 99%

“…In Drosophila a different role has been identified for dCRY (9 -11). It binds TIM and PER in a light-dependent manner (12,13). This interaction disrupts their inhibitory effect on transactivation of the CLOCK:CYC heterodimer, leading to a phase shift in circadian rhythm.…”

mentioning

confidence: 99%

Functional and Structural Analyses of Cryptochrome

Hirayama

Nakamura

Ishikawa

et al. 2003

Journal of Biological Chemistry

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Mouse mCRY1 and zebrafish zCRY1a and zCRY3 belong to the DNA photolyase/Cryptochrome family. mCRY1 and zCRY1a repress CLOCK:BMAL1-mediated transcription, whereas zCRY3 does not. Reciprocal chimeras between zCRY1a and zCRY3 were generated to determine the zCRY1a regions responsible for nuclear translocation, interaction with the CLOCK:BMAL1 heterodimer, and repression of CLOCK:BMAL1-mediated transcription. Three regions, RD-2a-(126 -196), RD-1-(197-263), and RD-2b-(264 -293), were identified. Proteins in this family consist of an N-terminal ␣/␤ domain and a C-terminal helical domain connected by an interdomain loop. RD-2a is within this loop, RD-1 is at the N-terminal 50 amino acids, and RD-2b at the following 31 amino acid residues of the helical domain. Either RD-2a or RD-1 is required for interaction with the CLOCK: BMAL1 heterodimer, and either RD-1 or RD-2b is required for the nuclear translocation of CRY. Both of these functions are prerequisites for the transcriptional repressor activity. The functional nuclear localizing signal in the RD-2b region also was identified. The sequence is well conserved among repressor-type CRYs, including mCRY1. Mutations in the nuclear localizing signal of mCRY1 reduce the extent of its nuclear localization. These findings show that both nuclear localization and interaction with the CLOCK:BMAL heterodimer are essential for transcriptional repression by CRY.Organisms ranging from bacteria to humans have daily rhythms driven by endogenous oscillators called circadian clocks that regulate various biochemical, physiological, and behavioral processes with a periodicity of approximate by 24 h (1-3). Under natural conditions, rhythms are entrained to a 24-h day by environmental time cues, most commonly light. These circadian clock mechanisms have been investigated by characterizing the "clock genes" that affect the daily rhythm. The core of the clock mechanisms in Drosophila, Neurospora, mammals, and cyanobacteria is expressed by a transcription/ translation-based negative feedback loop that relies on positive and negative oscillator elements. The negative feedback loop begins by activating the transcription of clock genes, the products of which then negatively regulate their own expression, setting up the rhythmic oscillations of gene expression that drive the circadian clock. Although negative feedback loop is a common mechanism in Drosophila, Neurospora, mammals, and cyanobacteria, its components differ with the species. Drosophila and mammals have common components (orthologous gene products), except for the negative elements TIM 1 (TIMELESS) and CRY (Cryptochrome). PER (PERIOD), and TIM, identified as the negative elements in Drosophila, form a heterodimer that translocates to the nucleus where its components interact with the positive elements dCLOCK and CYC (4). Formation of a complex decreases dCLOCK:CYC-mediated transcription, resulting in the repression of expression (5, 6). In mammals, CRY1 and CRY2 are partners of the PER heterodimer, rather than TIM. In mammals, the mP...

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“…The other way is through the cryptochrome (cry) gene that encodes a bluelight-sensitive molecule mentioned earlier. CRY is activated by light, and binds to both TIM and PER 60,61 in transient interactions that are difficult to capture in vivo. 62 A consequence of the activation of CRY is that it precedes light-induced TIM ubiquitination and degradation.…”

Section: How the Clock Responds To Lightmentioning

confidence: 99%

Molecular genetics of the fruit-fly circadian clock

2006

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The circadian clock percolates through every aspect of behaviour and physiology, and has wide implications for human and animal health. The molecular basis of the Drosophila circadian clock provides a model system that has remarkable similarities to that of mammals. The various cardinal clock molecules in the fly are outlined, and compared to those of their actual and 'functional' homologues in the mammal. We also focus on the evolutionary tinkering of these clock genes and compare and contrast the neuronal basis for behavioural rhythms between the two phyla.

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Light-dependent interaction between Drosophila CRY and the clock protein PER mediated by the carboxy terminus of CRY

Abstract: This study shows that, as in mammals, Drosophila CRY interacts with PER, and, as in plants, the C terminus of CRY is involved in mediating light responses. A model for the light dependence of CRY is discussed.

Cited by 134 publications

References 24 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

Functional and Structural Analyses of Cryptochrome

Molecular genetics of the fruit-fly circadian clock

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