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Published on: November 11, 2016
Casein kinase 1 promotes synchrony of the circadian clock network
Abstract:
Casein kinase 1, known as DOUBLETIME (DBT) in Drosophila melanogaster, is a critical component of the circadian clock that phosphorylates and promotes degradation of the PERIOD (PER) protein. However, other functions of DBT in circadian regulation are not clear, in part because severe reduction of dbt causes preadult lethality. Here we report the molecular and behavioral phenotype of a viable dbt(EY02910) loss-of-function mutant. We found that DBT protein levels are dramatically reduced in adult dbt(EY02910) flies, and the majority of mutant flies display arrhythmic behavior, with a few showing weak, long-period (∼32 h) rhythms. Peak phosphorylation of PER is delayed, and both hyper- and hypophosphorylated forms of the PER and CLOCK proteins are present throughout the day. In addition, molecular oscillations of the circadian clock are dampened. In the central brain, PER and TIM expression is heterogeneous and decoupled in the canonical clock neurons of the dbt(EY02910) mutants. We also report an interaction between dbt and the signaling pathway involving pigment dispersing factor (PDF), a synchronizing peptide in the clock network. These data thus demonstrate that overall reduction of DBT causes long and arrhythmic behavior, and they reveal an unexpected role of DBT in promoting synchrony of the circadian clock network.
Insights
The DOUBLETIME (DBT) protein is crucial for fruit fly circadian rhythms. Reduced DBT levels disrupt the PER protein cycle, leading to arrhythmic behavior and desynchronized clock neurons.
Area of Science:
- Chronobiology
- Molecular Biology
- Genetics
Background:
- Casein kinase 1, known as DOUBLETIME (DBT) in Drosophila, is essential for circadian clock function.
- DBT phosphorylates and degrades PERIOD (PER) protein, but its broader roles are unclear due to lethality in severe mutants.
Purpose of the Study:
- Investigate the molecular and behavioral effects of a viable dbt loss-of-function mutant.
- Elucidate the role of DBT in circadian rhythm regulation and network synchrony.
Main Methods:
- Analysis of a viable dbt(EY02910) loss-of-function mutant in Drosophila melanogaster.
- Assessment of DBT protein levels, PER and CLOCK protein phosphorylation, and molecular oscillations.
- Examination of PER and TIM expression in clock neurons and interaction with PDF signaling.
Main Results:
- DBT protein levels were significantly reduced in adult mutant flies.
- Mutant flies exhibited predominantly arrhythmic behavior, with some showing long-period (∼32 h) rhythms.
- PER phosphorylation was delayed, molecular clock oscillations were dampened, and PER/TIM expression was heterogeneous and decoupled in clock neurons.
Conclusions:
- Reduced DBT levels cause long and arrhythmic circadian behavior in fruit flies.
- DBT plays a critical role in maintaining the synchrony of the circadian clock network.
- DBT interacts with the PDF signaling pathway, highlighting its role in network coordination.
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