A Posttranslational Chemical Circadian Oscillator in Cyanobacteria

  • Hideo Iwasaki

To understand dynamic biological behaviors at the system level in the “post-genome” era, it is important to elucidate the complicated molecular network generating biological information in addition to classical analysis on a single gene—function relationship. Periodic temporal (rhythmic) and spatial (morphological) pattern formations are both typical examples of dynamic and complex phenomena widely observed in organisms from bacteria to plants and humans. To elucidate such spatiotemporal dynamics at the molecular systems level, integration of molecular genetics, molecular biology, biochemistry, comprehensive genomic and post-genomic approaches, quantitative analyses, and mathematical considerations is necessary. In addition, synthetic biological approaches to reconstitute such phenomena in vitro and/or in vivo are also helpful to validate reality and find problems in the proposed molecules or models. For this type of analysis, we have analyzed cyanobacteria as one of the simplest organisms to exhibit circadian rhythms and regular pattern formations with cell differentiation. Here, I summarize a brief history and the current state of molecular, biochemical, and synthetic analysis on the cyanobacterial circadian clock and refer to some prospects on extensive researches on morphological development in filamentous cyanobacteria.


Circadian Rhythm Circadian Clock Circadian Timing Clock Protein Synechococcus Elongatus 
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  1. Dunlap JC (2004) The molecular mechanism of circadian oscillators. In: Chronobiology:Biological Timekeeping. Sinauer Associates, Sunderland, MA, pp 212–253Google Scholar
  2. Golden JW, Yoon HS (2003) Heterocyst development in Anabaena. Curr Opin Microbiol 6:557–563PubMedCrossRefGoogle Scholar
  3. Goodwin BC (1965) Oscillatory behavior in enzymatic control processes. Adv Enzyme Regul 3:425–438PubMedCrossRefGoogle Scholar
  4. Grobbelaar N, Huang T-C, Lin H-Y, Chow T-J (1986) Dinitrogen-fixing endogenous rhythm in Synechococcus RF-1. FEMS Microbiol Lett 37:173–177CrossRefGoogle Scholar
  5. Hardin PE, Hall JC, Rosbash M (1990) Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature (Lond) 343:536–540CrossRefGoogle Scholar
  6. Hirata H, Yoshiura S, Ohtsuka T, Bessho Y, Harada T, Yoshikawa K, Kageyama R (2002) Oscillatory expression of the bHLH factor Hes1 regulated by a negative feedback loop. Science 298:840–843PubMedCrossRefGoogle Scholar
  7. Ishiura M, Kutsuna S, Aoki S, Iwasaki H, Andersson CR, Tanabe A, Golden SS, Johnson CH, Kondo T (1998) Expression of a gene cluster kaiABC as a circadian feedback process in cyano-bacteria. Science 281:1519–1523PubMedCrossRefGoogle Scholar
  8. Iwasaki H, Dunlap JC (2000) Microbial circadian oscillatory systems in Neurospora and Synechococcus: models for cellular clocks. Curr Opin Microbiol 3:189–196PubMedCrossRefGoogle Scholar
  9. Iwasaki H, Kondo T (2000) The current state and problems of circadian clock studies in cyano-bacteria. Plant Cell Physiol 41:1013–1020PubMedCrossRefGoogle Scholar
  10. Iwasaki H, Kondo T (2004) Circadian timing mechanism in the prokaryotic clock system of cyanobacteria. J Biol Rhythms 19:436–444PubMedCrossRefGoogle Scholar
  11. Iwasaki H, Taniguchi Y, Ishiura M, Kondo T (1999) Physical interactions among circadian clock proteins, KaiA, KaiB and KaiC, in cyanobacteria. EMBO J 18:1137–1145PubMedCrossRefGoogle Scholar
  12. Iwasaki H, Williams SB, Kitayama Y, Ishiura M, Golden SS, Kondo T (2000) A KaiC-interacting sensory histIDine kinase, SasA, necessary to sustain robust circadian oscillation in cyanobacteria. Cell 101:223–233PubMedCrossRefGoogle Scholar
  13. Iwasaki H, Nishiwaki T, Kitayama Y, Nakajima M, Kondo T (2002) KaiA-stimulated KaiC phosphorylation in circadian timing loops in cyanobacteria. Proc Natl Acad Sci USA 99:15788–15793PubMedCrossRefGoogle Scholar
  14. Kageyama H, Kondo T, Iwasaki H (2003) Circadian formation of clock protein complexes by KaiA, KaiB, KaiC, and SasA in cyanobacteria. J Biol Chem 278:2388–2395PubMedCrossRefGoogle Scholar
  15. Kageyama H, Nishiwaki T, Nakajima M, Iwasaki H, Oyama T, Kondo T (2006) Cyanobacterial circadian pacemaker: Kai protein complex dynamics in the KaiC phosphorylation cycle in vitro. Mol Cell 23:161–171PubMedCrossRefGoogle Scholar
  16. Kitayama Y, Iwasaki H, Nishiwaki T, Kondo T (2003) KaiB functions as an attenuator of KaiC phosphorylation in the cyanobacterial clock system. EMBO J 22:2127–2134PubMedCrossRefGoogle Scholar
  17. Kitayama Y, Nishiwaki T, Terauchi K, Kondo T (2008) Dual KaiC-based oscillations constitute the circadian system of cyanobacteria. Genes Dev 22:1513–1521PubMedCrossRefGoogle Scholar
  18. Kondo T, Strayer CA, Kulkarni RD, Taylor W, Ishiura M, Golden SS, Johnson CH (1993) Circadian rhythms in prokaryotes: luciferase as a reporter of circadian gene expression in cyanobacteria. Proc Natl Acad Sci USA 90:5672–5676PubMedCrossRefGoogle Scholar
  19. Konopka RJ, Benzer S (1971) Clock mutants of Drosophila melanogaster. Proc Natl Acad Sci USA 68:2112–2116PubMedCrossRefGoogle Scholar
  20. Liu Y, Tsinoremas NF, Johnson CH, Lebedeva NV, Golden SS, Ishiura M, Kondo T (1995) Circadian orchestration of gene expression in cyanobacteria. Genes Dev 9:1469–1478PubMedCrossRefGoogle Scholar
  21. Mitsui A, Kumazawa S, Takahashi A, Ikemoto H, Cao S, Arai T (1986) Strategy by which nitrogen-fixing unicellular cyanobacteria grow photoautotrophically. Nature (Lond) 323:720–722.CrossRefGoogle Scholar
  22. Mori T, Saveliev SV, Xu Y, Stafford WF, Cox MM, Inman RB, Johnson CH (2002) Circadian clock protein KaiC forms ATP-dependent hexameric rings and binds DNA. Proc Natl Acad Sci USA 99:17203–7208PubMedCrossRefGoogle Scholar
  23. Nakajima M, Imai K, Ito H, Nishiwaki T, Murayama Y, Iwasaki H, Oyama T, Kondo T (2005) Reconstitution of circadian oscillation of cyanobacterial KaiC phosphorylation in vitro. Science 308:414–415PubMedCrossRefGoogle Scholar
  24. Nishiwaki T, Iwasaki H, Ishiura M, Kondo T (2000) NucleotIDe binding and autophosphorylation of clock protein KaiC as a circadian timing process of cyanobacteria. Proc Natl Acad Sci USA 97:495–499PubMedCrossRefGoogle Scholar
  25. Stal LJ, Krumbein WE (1985) Nitrogenase activity in the non-heterocystous cyanobacterium Oscillatoria sp. grown under alternating light-dark cycles. Arch Microbiol 143:67–71CrossRefGoogle Scholar
  26. Takai N, Nakajima M, Oyama T, Kito R, Sugita C, Sugita M, Kondo T, Iwasaki H (2006) A KaiC-associating SasA—RpaA two-component regulatory system as a major circadian timing mediator in cyanobacteria. Proc Natl Acad Sci USA 103:12109–12114PubMedCrossRefGoogle Scholar
  27. Terauchi K, Kitayama Y, Nishiwaki T, Miwa K, Murayama Y, Oyama T, Kondo T (2007) ATPase activity of KaiC determines the basic timing for circadian clock of cyanobacteria. Proc Natl Acad Sci USA 104:16377–16381PubMedCrossRefGoogle Scholar
  28. Tomita J, Nakajima M, Kondo T, Iwasaki H (2005) No transcription–translation feedback in cir-cadian rhythm of KaiC phosphorylation. Science 307:251–254PubMedCrossRefGoogle Scholar
  29. Ueda HR, Hayashi S, Chen W, Sano M, MachIDa M, Shigeyoshi Y, Iino M, Hashimoto S (2005) System-level IDentification of transcriptional circuits underlying mammalian circadian clocks. Nat Genet 37:187–192PubMedCrossRefGoogle Scholar
  30. Williams SB, Vakonakis I, Golden SS, LiWang AC (2002) Structure and function from the circa-dian clock protein KaiA of Synechococcus elongatus: a potential clock input mechanism. Proc Natl Acad Sci USA 99:15357–15362PubMedCrossRefGoogle Scholar
  31. Zhang CC, Laurent S, Sakr S, Peng L, Bédu S (2006) Heterocyst differentiation and pattern formation in cyanobacteria: a chorus of signals. Mol Microbiol 59:367–375PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2009

Authors and Affiliations

  • Hideo Iwasaki
    • 1
  1. 1.Department of Electrical Engineering & BioscienceWaseda University, and PRESTO, Japan Science & Technology Agency (JST)ShinjukuJapan

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