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Cyanobacterial circadian clocks — timing is everything

Key Points

  • Behavioural and physiological processes of numerous organisms are controlled by a circadian clock. Of these, the simplest model system to uncover the workings of these rhythms is the unicellular cyanobacterium, Synechococcus elongatus PCC 7942.

  • Automated detection of circadian expression from luciferase gene fusions allows for large-scale mutant hunts to identify necessary components of the bacterial clock.

  • A locus of three genes — kaiA, kaiB, and kaiC — was found to encode the core of the clock. Mutation of any of these genes results in altered circadian rhythms, including arrhythmicity and short or long periods.

  • Each Kai protein interacts with itself and with each of the other Kai proteins.

  • Functions have been assigned to KaiA and KaiB on the basis of their effects on the phosphorylation state of KaiC — KaiA stimulates KaiC autophosphorylation and KaiB abrogates the positive effect of KaiA.

  • CikA and LdpA interpret environmental input as timing cues to reset the clock to local time or to fine-tune the period of the rhythm under varying light intensities, respectively.

  • The SasA protein closely associates with the central Kai proteins and transduces temporal information to cellular processes that are under circadian control.

  • The Kai proteins and SasA are co-purified in large macromolecular complexes during the night. The abundance of each protein, as well as the size of the complex, changes with the light/dark cycle.

Abstract

For more than three billion years, the organisms on this planet have known, like Little Orphan Annie, that “The sun'll come out tomorrow”, and many have honed their biochemistry to exploit this knowledge. The cyanobacteria have had ample time to fashion a suitable timepiece, as they are among the oldest inhabitants of the earth. For these organisms, light is food, and it is a nutrient that shows up at the same time every day. Not surprisingly, cyanobacteria have learned to arrange their days around dinnertime.

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Figure 1: Fundamental properties of a circadian rhythm.
Figure 2: Tools of the trade.
Figure 3: A cyanobacterial clock model.
Figure 4: Persistence of rhythmic gene expression in constant light.

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Acknowledgements

We gratefully acknowledge the contributions of past and current members of the Golden lab, and in particular thank E. M. Clerico for the data in Figure. 4. We also thank J. L. Ditty, N. Ivleva, H. Iwasaki, M. Katayama, T. Kondo, A. LiWang, M. Sugita, J. Vakonakis, and S. B. Williams for sharing unpublished information, and P. A. Youderian for initiating the functional genomics project. Our work on S. elongatus circadian rhythms and functional genomics is supported by grants from the National Institutes of Health, National Science Foundation and Department of Energy to S. S. G.

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Correspondence to Susan S. Golden.

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DATABASES

Entrez

MIT 9313

LocusLink

Cryptochrome

period

SwissPort

CikA

D1

CLOCK

CYCLE

FREQUENCY

KaiA

KaiB

KaiC

SasA

WHITE COLLAR-1

FURTHER INFORMATION

Susan S. Golden's laboratory

Gloeobacter genome

S. elongatus PCC 7942 genome

Glossary

OSCILLATOR

In circadian biology, it is a subset of genes and their protein products that are sufficient to produce a circadian rhythm of activity.

WALKER A MOTIF

A motif (GXXXGKT), where X is any amino acid residue, that is involved in nucleotide-binding of many ATP-requiring enzymes.

'TWO-COMPONENT' REGULATORY SYSTEMS

A signal-transduction system using two components — a histidine protein kinase (HPK) and a response regulator (RR) — to sense and respond to external stimuli. HPKs autophosphorylate at a histidyl residue after stimulation and transfer that phosphoryl group to a cognate RR at its aspartyl residue to induce a conformational change in the regulatory domain, which, in turn, activates an associated domain.

PSEUDO-RECEIVER

A protein with sequence or structural similarity to the receiver domains of response regulator proteins, but that lacks the aspartyl residue necessary for accepting a phosphoryl group.

GAF MOTIF

A ubiquitous motif, found in sensory proteins of both prokaryotic and eukaryotic cells, that performs a multitude of functions, including bilin lyase activity in bacteriophytochromes of cyanobacteria.

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Golden, S., Canales, S. Cyanobacterial circadian clocks — timing is everything. Nat Rev Microbiol 1, 191–199 (2003). https://doi.org/10.1038/nrmicro774

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