Phosphorylation of PERIOD Is Influenced by Cycling Physical Associations of DOUBLE-TIME, PERIOD, and TIMELESS in the Drosophila Clock

Kloss, Brian; Rothenfluh, Adrian; Young, Michael W.; Sáez, Lino

doi:10.1016/s0896-6273(01)00320-8

Cited by 162 publications

(177 citation statements)

References 29 publications

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“…In the heads of wild-type adults challenged with a 1808 phase shift in their environmental temperature cycle, per transcript reacted quickly with an increase in rhythmic amplitude and an apparent advance in phase, whereas about 20 h later both a phase advance in tim transcript and a phase delay in PER and TIM protein were initiated. tim and per mRNA and protein rhythms are known to be functionally linked in the circadian cycle in a number of ways: (i) of course, PER and TIM protein are produced from per and tim transcript; (ii) TIM protein is known to stabilize PER protein by preventing DOUBLETIME-mediated phosphorylation and subsequent turnover of PER protein [31]; and (iii) PER and TIM feedback negatively on the expression of per and tim transcripts via PER-mediated inhibition of the CLK/CYC transcription factor [32]. As per transcript is the first to show temperature-mediated resetting, its response cannot be a secondary consequence of a phase shift in tim transcript or PER or TIM protein.…”

Section: Discussionmentioning

confidence: 99%

Temperature-dependent resetting of the molecular circadian oscillator inDrosophila

2014

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Circadian clocks responsible for daily time keeping in a wide range of organisms synchronize to daily temperature cycles via pathways that remain poorly understood. To address this problem from the perspective of the molecular oscillator, we monitored temperature-dependent resetting of four of its core components in the fruitfly Drosophila melanogaster: the transcripts and proteins for the clock genes period ( per) and timeless (tim). The molecular circadian cycle in adult heads exhibited parallel responses to temperature-mediated resetting at the levels of per transcript, tim transcript and TIM protein. Early phase adjustment specific to per transcript rhythms was explained by clockindependent temperature-driven transcription of per. The cold-induced expression of Drosophila per contrasts with the previously reported heatinduced regulation of mammalian Period 2. An altered and more readily reentrainable temperature-synchronized circadian oscillator that featured temperature-driven per transcript rhythms and phase-shifted TIM and PER protein rhythms was found for flies of the 'Tim 4' genotype, which lacked daily tim transcript oscillations but maintained post-transcriptional temperature entrainment of tim expression. The accelerated molecular and behavioural temperature entrainment observed for Tim 4 flies indicates that clock-controlled tim expression constrains the rate of temperature cycle-mediated circadian resetting.

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Section: Discussionmentioning

confidence: 99%

Temperature-dependent resetting of the molecular circadian oscillator inDrosophila

2014

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“…dbt is expressed throughout the circadian cycle. Nevertheless, in lateral neurons and in photoreceptor cells, DBT is nuclear in per and tim null mutants and shows a circadian subcellular distribution, cycling between the cytoplasm and nucleus in a fashion that parallels the behavior of PER accumulation in wild-type fly heads (Kloss et al 2001). In vivo, DBT physically interacts with PER but is only found associated with TIM in PER/TIM complexes (Kloss et al 2001).…”

Section: Dbt a Nuclear Protein Is Retained By Per In The Cytoplasm mentioning

confidence: 98%

“…We next focused our attention on DBT, another clock protein that associates with PER and the PER/TIM complex (Kloss et al , 2001. dbt is expressed throughout the circadian cycle.…”

Section: Dbt a Nuclear Protein Is Retained By Per In The Cytoplasm mentioning

confidence: 99%

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A PER/TIM/DBT Interval Timer forDrosophila's Circadian Clock

Sáez¹,

Meyer²,

Young³

2007

Cold Spring Harbor Symposia on Quantitative Biology

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Circadian rhythms in Drosophila are supported by a negative feedback loop, in which PERIOD (PER) and Timeless (TIM) shut down their own transcription as they translocate once a day from the cytoplasm of clock-containing cells to the nucleus. Period length is partially determined by an interval of cytoplasmic retention of the TIM and PER proteins. To study this process, we examined PER/TIM/Doubletime (DBT) physical interactions and nuclear translocation by imaging individual cultured Drosophila cells. Using live cell video microscopy and green fluorescent protein (GFP) tags, we observed dynamic patterns of stability and localization for DBT, PER, and TIM that resembled those previously found in vivo. These studies suggest that a cytoplasmic interval timer regulates nuclear translocation of these proteins. The cultured cell assay provides a potent system to study interactions among new and known genes involved in the generation of circadian behavior.

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“…PEST-1 is phosphorylated in vitro by casein kinase 1a (CK-1a) . Neurospora CK-1a is the homolog of Drosophila DOUBLE-TIME and mammalian CKI /␦, which are both essential for circadian rhythmicity in flies and mammals (Kloss et al , 2001Price et al 1998;Lowrey et al 2000;Vielhaber et al 2000;Lee et al 2001).…”

Section: Physical Properties Of Frqmentioning

confidence: 99%

Transcriptional and post-transcriptional regulation of the circadian clock of cyanobacteria and Neurospora

Brunner¹,

Schafmeier²

2006

Genes Dev.

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Circadian clocks are self-sustained oscillators modulating rhythmic transcription of large numbers of genes. Clock-controlled gene expression manifests in circadian rhythmicity of many physiological and behavioral functions. In eukaryotes, expression of core clock components is organized in a network of interconnected positive and negative feedback loops. This network is thought to constitute the pacemaker that generates circadian rhythmicity. The network of interconnected loops is embedded in a supra-net via a large number of interacting factors that affect expression and function of core clock components on transcriptional and post-transcriptional levels. In particular, phosphorylation and dephosphorylation of clock components are critical processes ensuring robust self-sustained circadian rhythmicity and entrainment of clocks to external cues. In cyanobacteria, three clock proteins have the capacity to generate a self-sustained circadian rhythm of autophosphorylation and dephosphorylation independent of transcription and translation. This phosphorylation rhythm regulates the function of these clock components, which then facilitate rhythmic gene transcription, including negative feedback on their own genes. In this article, we briefly present the mechanism of clock function in cyanobacteria. We then discuss in detail the contribution of transcriptional feedback and protein phosphorylation to various functional aspects of the circadian clock of Neurospora crassa.Circadian rhythms are found in numerous light-perceiving organisms including cyanobacteria, algae, fungi, plants, insects, and vertebrates. The rhythms are supported by cell-autonomous circadian clocks, which regulate expression of a large number of genes on the level of transcription (for review, see Transcriptional/translational feedback loops are hallmarks of circadian clocks in all organisms. In eukaryotes, expression of core clock components is organized in a complex network of interconnected positive and negative feedback loops (for review, see Dunlap and Loros 2004;Gachon et al. 2004;Hardin 2005). This network of gene expression is assumed to generate circadian rhythmicity. Elimination of key components of these interconnected loops disrupts many, if not all, rhythmic outputs, depending on the organism. Expression, subcellular localization, assembly, function, and turnover of clock components are crucial for circadian rhythmicity, and thus, the core clock is embedded in a supra-net of cellular machinery regulating various aspects of clock function. Protein phosphorylation and dephosphorylation are important regulatory mechanisms that are critical for self-sustained circadian rhythmicity and entrainment of clocks to external cues. It is unclear to what extent reversible phosphorylations are mechanistically instrumental for generation of rhythmicity in eukaryotic clocks.Recent findings have shown that clock proteins in cyanobacteria generate a self-sustained circadian rhythm of autophosphorylation and dephosphorylation, which is independent of tra...

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Phosphorylation of PERIOD Is Influenced by Cycling Physical Associations of DOUBLE-TIME, PERIOD, and TIMELESS in the Drosophila Clock

Cited by 162 publications

References 29 publications

Temperature-dependent resetting of the molecular circadian oscillator inDrosophila

Temperature-dependent resetting of the molecular circadian oscillator inDrosophila

A PER/TIM/DBT Interval Timer forDrosophila's Circadian Clock

Transcriptional and post-transcriptional regulation of the circadian clock of cyanobacteria and Neurospora

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