Suppression of PERIOD protein abundance and circadian cycling by the Drosophila clock mutation timeless.

Price, Jeffrey L.; Dembinska, Marie E.; Young, Michael W.; Rosbash, Michael

doi:10.1002/j.1460-2075.1995.tb00075.x

Cited by 191 publications

(168 citation statements)

References 41 publications

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“…Instead, the PER protein profile resembles that of TIM protein during temperature-mediated re-entrainment. Indeed, this would be predicted based on the requirement for TIM to stabilize PER [24]. The delayed temperature-dependent phase advancing of tim transcript also does not obviously result from the changes in either per transcript or PER or TIM protein.…”

Section: Discussionmentioning

confidence: 95%

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: 95%

Temperature-dependent resetting of the molecular circadian oscillator inDrosophila

2014

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“…The stabilizing effect of TIM most likely involves a change in the phosphorylation state of PER: It may down-regulate kinase activity on PER or up-regulate phosphatase activity. A similar situation occurs in flies where PER depends on TIM for stability, but the mechanisms involved are not known (Price et al 1995).…”

Section: Molecular Basis Of the Clockmentioning

confidence: 94%

Molecular Analysis of Sleep: Wake Cycles inDrosophila

Sehgal¹,

Joiner²,

Crocker³

et al. 2007

Cold Spring Harbor Symposia on Quantitative Biology

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“…Subsequently it was shown that the PER and TIM proteins physically interact in vitro, in yeast and Drosophila cells (Gekakis et al 1995;Saez and Young 1996). Interdependent functions of per and tim were also indicated by the finding that PER and TIM coexpression was required for the nuclear accumulation of either protein, and that PER stability was dependent on TIM (Vosshall et al 1994;Price et al 1995;Hunter-Ensor et al 1996;Myers et al 1996). Thus, with the discovery of tim and the regulated nuclear accumulation of PER and TIM (see also Curtin et al 1995), a model was proposed that incorporated the concept of a specific temporal delay to explain how negative feedback could generate oscillations in gene expression.…”

Section: Timeless and Temporal Delays In The Circadian Clockmentioning

confidence: 99%

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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Suppression of PERIOD protein abundance and circadian cycling by the Drosophila clock mutation timeless.

Abstract: The timeless mutation (tim)

Cited by 191 publications

References 41 publications

Temperature-dependent resetting of the molecular circadian oscillator inDrosophila

Temperature-dependent resetting of the molecular circadian oscillator inDrosophila

Molecular Analysis of Sleep: Wake Cycles inDrosophila

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

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