Functional Analysis of Casein Kinase 1 in a Minimal Circadian System

Ooijen, Gerben van; Hindle, Matthew; Martin, Susan D.; Barrios-Llerena, Martin E.; Sanchez, Frédéric; Bouget, François‐Yves; O’Neill, John S.; Bihan, Thierry Le; Millar, Andrew J.

doi:10.1371/journal.pone.0070021

Cited by 40 publications

(71 citation statements)

References 61 publications

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“…In all cases, a statistically significant long-period phenotype was observed (Figure 2A,B), associated with an approximately 2-fold overexpression level (Figure 2C). The period lengthening that was observed upon overexpression of CK1 tau was in the same range as that resulting from overexpression of the wild-type CK1 allele (Figure 2D) averaged for 6 independent overexpression lines previously published [18]. This result shows that the effects of both alleles on period lengthening are very similar.…”

Section: Resultssupporting

confidence: 82%

“…An initial phase advance is observed upon IC261 treatment, followed by a dose-dependent long period rhythm in the parent line (Figure 3A, B). The period-lengthening effect of IC261 is indeed decreased in CK1 tau -OX21 compared to the CK1-OX line (Figure 3A, C), similarly to the result obtained with overexpression of the wild-type allele (Figure 3A and [18]).…”

Section: Resultssupporting

confidence: 80%

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Functional analysis of the rodent CK1tau mutation in the circadian clock of a marine unicellular alga

et al. 2013

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BackgroundCasein Kinase 1 (CK1) is one of few proteins known to affect cellular timekeeping across metazoans, and the naturally occurring CK1tau mutation shortens circadian period in mammals. Functional conservation of a timekeeping function for CK1 in the green lineage was recently identified in the green marine unicell Ostreococcus tauri, in spite of the absence of CK1's transcriptional targets known from other species. The short-period phenotype of CK1tau mutant in mammals depends specifically on increased CK1 activity against PERIOD proteins. To understand how CK1 acts differently upon the algal clock, we analysed the cellular and proteomic effects of CK1tau overexpression in O. tauri.ResultsOverexpression of the CK1tau in O. tauri induces period lengthening identical to overexpression of wild-type CK1, in addition to resistance to CK1 inhibitor IC261. Label-free quantitative mass spectrometry of CK1tau overexpressing algae revealed a total of 58 unique phospho-sites that are differentially responsive to CK1tau. Combined with CK1 phosphorylation site prediction tools and previously published wild-type CK1-responsive peptides, this study results in a highly stringent list of upregulated phospho-sites, derived from proteins containing ankyrin repeats, kinase proteins, and phosphoinositide-binding proteins.ConclusionsThe identical phenotype for overexpression of wild-type CK1 and CK1tau is in line with the absence of critical targets for rodent CK1tau in O. tauri. Proteomic analyses reveal that two thirds of previously reported CK1 overexpression-responsive phospho-sites are shared with CK1tau. These results indicate that the two alleles are functionally indiscriminate in O. tauri, and verify the identified cellular CK1 target proteins in a minimal circadian model organism.

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Section: Resultssupporting

confidence: 82%

Section: Resultssupporting

confidence: 80%

Functional analysis of the rodent CK1tau mutation in the circadian clock of a marine unicellular alga

et al. 2013

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“…Regardless, the data indicate that changes in CK1 activity, perhaps in response to peptidergic signals including PDF or VIP, mediate communication across the circadian network. Intriguingly, a recent study using the unicellular marine alga Ostreococcus tauri indicated that CK1 activity is circadian gated (54), which could also be the case in higher organisms.…”

Section: Ey02910mentioning

confidence: 96%

Casein Kinase 1 Promotes Synchrony of the Circadian Clock Network

Zheng

Sowcik

Chen

et al. 2014

Molecular and Cellular Biology

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bCasein 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 (ϳ32 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. In Drosophila melanogaster, daily rhythmic behavior is governed by a network of ϳ150 brain clock neurons (1, 2), each of which contains a molecular oscillator (3). Within this oscillator, the CLOCK (CLK) and CYCLE (CYC) proteins activate transcription of the repressor genes period (per) and timeless (tim) during the day, and accumulated PER and TIM proteins repress the transcriptional activity of CLK-CYC in the late night/early morning. Phosphorylation of clock proteins, which is mainly regulated by casein kinases (CK1 and CK2) (4-6), glycogen synthase kinase 3 beta (GSK3␤) (7), and specific protein phosphatases (8, 9), plays a pivotal role in circadian timing, at least in part by regulating the stability and nuclear localization of PER and TIM (3).Robust circadian behavior relies on the coupling of clock neurons within the network. The neuropeptide pigment dispersing factor (PDF) is required for synchrony of the circadian clock circuit and its output (10-12). A similar framework operates in the mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN), where a peptide, vasoactive intestinal polypeptide (VIP), released by some clock cells, synchronizes individual oscillators to generate a coherent output (13,14). How PDF and VIP synchronize the circadian clock network and its output is unclear. Interestingly, in Ck1ε tau hamsters, there is a tissue-specific misalignment of some peripheral clocks with the SCN, suggesting that the tau mutation in CK1 causes a defect in synchronization (15). However, tau appears to be a gain-of-function mutation (16), and the redundancy of CK1 isoforms in mammals makes it difficult to address consequences of CK1 loss.In Drosophila, Ck1ε is known as double-time (...

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“…In addition, casein kinase I is a component of fungal clocks (He et al, 2006). An algal clock, which does not require a transcriptional mechanism, is affected by CKI activity (van Ooijen et al, 2013). Cyanobacteria do not have a casein kinase I ortholog, but rhythmic phosphorylation of clock components is the central feature of the circadian mechanism (Nakajima et al, 2005).…”

Section: Introductionmentioning

confidence: 99%