Demasking biological oscillators: Properties and principles of entrainment exemplified by the
            <i>Neurospora</i>
            circadian clock

Roenneberg, Till; Dragovic, Zdravko; Merrow, Martha

doi:10.1073/pnas.0501884102

Cited by 90 publications

(107 citation statements)

References 44 publications

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“…Yet, partial or residual functions of the frq-based oscillator, in particular temperature-entrainable rhythmicity of conidiation, can also be observed in frq-deficient mutants, suggesting that additional oscillatory systems substitute for frq under specific conditions (Merrow et al 1999;Correa et al 2003;Pregueiro et al 2005;Roenneberg et al 2005). Components of such frq-less oscillators (FLOs) are not yet identified.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

confidence: 99%

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

Brunner¹,

Schafmeier²

2006

Genes Dev.

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“…The entrainment of a frequency-less oscillator in Neurospora crassa has been the subject of some recent debate (21,22,29), and the parallels with a residual rhythmicity in per-null Drosophila are striking. Furthermore, the rescue of per 01 behavior by cry b would appear, at least superficially, to be similar to the situation in mammals in which a Cry mutation restores free-running rhythms to the arrhythmic mPer2 mutant mouse (9); this has been explained in terms of the freeing up in the double mutant of other mPer and Cry paralogues to interact and restore the original behavior.…”

Section: Discussionmentioning

confidence: 99%

Disruption of Cryptochrome partially restores circadian rhythmicity to the arrhythmic period mutant of Drosophila

Collins

Dissel

Gaten

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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The Drosophila melanogaster circadian clock is generated by interlocked feedback loops, and null mutations in core genes such as period and timeless generate behavioral arrhythmicity in constant darkness. In light-dark cycles, the elevation in locomotor activity that usually anticipates the light on or off signals is severely compromised in these mutants. Light transduction pathways mediated by the rhodopsins and the dedicated circadian blue light photoreceptor cryptochrome are also critical in providing the circadian clock with entraining light signals from the environment. The cry b mutation reduces the light sensitivity of the fly's clock, yet locomotor activity rhythms in constant darkness or light-dark cycles are relatively normal, because the rhodopsins compensate for the lack of cryptochrome function. Remarkably, when we combined a period-null mutation with cry b , circadian rhythmicity in locomotor behavior in light-dark cycles, as measured by a number of different criteria, was restored. This effect was significantly reduced in timeless-null mutant backgrounds. Circadian rhythmicity in constant darkness was not restored, and TIM protein did not exhibit oscillations in level or localize to the nuclei of brain neurons known to be essential for circadian locomotor activity. Therefore, we have uncovered residual rhythmicity in the absence of period gene function that may be mediated by a previously undescribed period-independent role for timeless in the Drosophila circadian pacemaker. Although we do not yet have a molecular correlate for these apparently iconoclastic observations, we provide a systems explanation for these results based on differential sensitivities of subsets of circadian pacemaker neurons to light.anticipation ͉ phase shift ͉ oscillator ͉ hourglass ͉ timeless T he PERIOD (PER) and TIMELESS (TIM) proteins are core components of the negative feedback loop that drives circadian oscillations in Drosophila. TIM stabilizes PER, and the PER and TIM proteins cooperate in nuclear entry and retention in key pacemaker cells at night (1). TIM degrades rapidly in response to light, releasing PER to repress per and tim transcription (1). D. melanogaster individuals carrying the null mutation per 01 display arrhythmic locomotor activity under constant darkness (DD), whereas in light-dark (LD) cycles, their locomotor activity is elevated under illumination and reduced in darkness, reflecting the ''masking'' effect of light (2, 3). Another mutation in the gene encoding the blue-light photoreceptor cryptochrome, cry b , gives attenuated light responses in a circadian context (4-7), but normal circadian locomotor behavior in 24-h LD cycles. As part of another study of seasonal behavioral responses to temperature and light effected via changes in per 3Ј splicing, we generated a per 01 ; cry b double mutant (8). We noted that a modest cycle in wild-type per 3Ј splicing in LD cycles at 29°C was exaggerated in per 01 and cry b mutants, yet in the double mutant, the amplitude of the splicing reverted back to ap...

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“…In Neurospora crassa, it has been a matter of controversial findings and discussions whether or not loss-of-function mutants of the central clock gene frequency (frq) can entrain to temperature cycles (Merrow et al 1999;Pregueiro et al 2005;Roenneberg et al 2005). Another way to address this question is to create a similar situation in a different organism, where it might be easier to obtain a clear answer.…”

Section: Clock Mutants and Temperature Entrainmentmentioning

confidence: 99%

Synchronization of theDrosophilaCircadian Clock by Temperature Cycles

Glaser

Stanewsky²

2007

Cold Spring Harbor Symposia on Quantitative Biology

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Demasking biological oscillators: Properties and principles of entrainment exemplified by the Neurospora circadian clock

Cited by 90 publications

References 44 publications

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

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

Disruption of Cryptochrome partially restores circadian rhythmicity to the arrhythmic period mutant of Drosophila

Synchronization of theDrosophilaCircadian Clock by Temperature Cycles

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