Dual Regulation with Ser/Thr Kinase Cascade and a His/Asp TCS in Myxococcus xanthus

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 631)


Fruiting body development of Myxococcus xanthus is propelled by temporal gene expression directed via stage-specific intercellular signaling pathways. M. xanthus exhibits social behaviors during its complex life cycle and is a potential source for production of natural products such as secondary metabolites. The numerous signaling pathways of M. xanthus consist of not only the two-component His-Asp phosphorelay system (TCS) but also protein Ser/Thr kinases (PSTKs) that regulate gene expression, motility and multicellular development. Recent studies have uncovered the unique molecular regulatory mechanism of MrpC, a transcription factor essential for fruiting body development and sporulation. mrpC expression is activated early in development by MrpB, which belongs to the NtrC family of TCS. MrpC, is, in turn, a transcriptional activator of fruA that encodes another key transcription factor, FruA. FruA is essential for fruiting body development and sporulation and regulates positively and negatively the synthesis of many developmental proteins. In addition, expression of mrpC during vegetative growth is kept at a low level by the PSTK Pkn8-Pkn 14 kinase cascade which negatively regulates MrpC-binding activity to its own promoter. Therefore, M. xanthus utilizes a novel dual system with both eukaryotic PSTK cascade and prokaryotic TCS signaling systems to tightly and precisely regulate MrpC levels, which activate timely fruA expression and propel fruiting body development and sporulation.


Vegetative Growth Histidine Kinase Kinase Cascade cAMP Receptor Protein Fruiting Body Formation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Parkinson JS. Signal transduction schemes of bacteria. Cell 1993; 73:857–871.PubMedCrossRefGoogle Scholar
  2. 2.
    Stock JB, Ninfa AJ, Stock AM. Protein phosphorylation and regulation of adaptive responses in bacteria. Microbiol Rev 1989; 53:450–490.PubMedGoogle Scholar
  3. 3.
    Dworkin M. (1996) Recent advances in the social and developmental biology of the Myxobacteria. Microbiol Rev 1996; 60:70–102.PubMedGoogle Scholar
  4. 4.
    Dworkin M, Kaiser D, eds. Myxobacteria II. American Society for Microbiology. Washington, DC: ASM Press, 1993.Google Scholar
  5. 5.
    Nariya H, Inouye S. An effective sporulation of Myxococcus xanthus requires glycogen consumption via Pkn4-activated 6-phosphofructose kinase. Mol Microbiol 2003; 49:517–528.PubMedCrossRefGoogle Scholar
  6. 6.
    Singer M, Kaiser D. Ectopic production of guanosine penta-and tetraphosphate can initiate early developmental gene expression in Myxococcus xanthus. Genes Dev 1995; 9:1633–1644.PubMedCrossRefGoogle Scholar
  7. 7.
    Harris BZ, Kaiser D, Singer M. The guanosine nucleotide (p)ppGpp initiates development and A-factor production in Myxococcus xanthus. Genes Dev 1998; 12:1022–1035.PubMedCrossRefGoogle Scholar
  8. 8.
    Shimkets LJ. Intercellular signaling during fruiting-body development of Myxococcus xanthus. Annu Rev Microbiol 1999; 53:525–549.PubMedCrossRefGoogle Scholar
  9. 9.
    Kaiser D. Signaling in myxobacteria. Annu Rev Microbiol 2004; 58:75–98.PubMedCrossRefGoogle Scholar
  10. 10.
    Kaplan HB, Plamann L. A Myxococcus xanthus cell density-sensing system required for multicellular development. FEMS Microbiol Lett 1996; 139:89–95.PubMedGoogle Scholar
  11. 11.
    Jelsbak L, Sogaard-Andersen L. Pattern formation by a cell surface-associated morphogen in Myxococcus xanthus. Proc Natl Acad Sci USA 2002; 99:2032–2037.PubMedCrossRefGoogle Scholar
  12. 12.
    Hagen TJ, Shimkets LJ. Nucleotide sequence and transcriptional products of the csg locus of Myxococcus xanthus. J Bacteriol 1990; 172:15–23.PubMedGoogle Scholar
  13. 13.
    Lee BU, Lee K, Mendez J et al. A tactile sensory system of Myxococcus xanthus involves an extracellular NAD(P)(+)-containing protein. Genes Dev 1995; 9:2964–2973.PubMedCrossRefGoogle Scholar
  14. 14.
    Lobedanz S, Søgaard-Andersen L. Identification of the C-signal, a contact-dependent morphogen coordinating multiple developmental responses in Myxococcus xanthus. Genes Dev 2003; 17:2151–2161.PubMedCrossRefGoogle Scholar
  15. 15.
    Keseler IM, Kaiser D. σ54, a vital protein for Myxococcus xanthus. Proc Natl Acad Sci USA 1997; 94:1979–1984.PubMedCrossRefGoogle Scholar
  16. 16.
    Jelsbak L, Givskov M, Kaiser D. Enhancer-binding proteins with a forkhead-associated domain and the sigma54 regulon in Myxococcus xanthus fruiting body development Proc Natl Acad Sci USA 2005; 102:3010–3015.PubMedCrossRefGoogle Scholar
  17. 17.
    Gorski L, Kaiser D. Targeted mutagenesis of sigma54 activator proteins in Myxococcus xanthus. J Bacteriol 1998; 180:5896–5905.PubMedGoogle Scholar
  18. 18.
    Sun H, Shi W. Genetic studies of mrp, a locus essential for cellular aggregation and sporulation of Myxococcus xanthus. J Bacteriol 2001; 183:4786–4795.PubMedCrossRefGoogle Scholar
  19. 19.
    Sun H, Shi W. Analyses of mrp genes during Myxococcus xanthus development. J Bacteriol 2001; 183:6733–6739.PubMedCrossRefGoogle Scholar
  20. 20.
    Caberoy NB, Welch RD, Jakobsen JS et al. Global mutational analysis of NtrC-like activators in Myxococcus xanthus: identifying activator mutants defective for motility and fruiting body development. J Bacteriol 2003; 185:6083–94.PubMedCrossRefGoogle Scholar
  21. 21.
    Kirby JR, Zusman DR. Chemosensory regulation of developmental gene expression in Myxococcus xanthus. Proc Natl Acad Sci USA 2003; 100:2008–2013.PubMedCrossRefGoogle Scholar
  22. 22.
    Ueki T, Inouye S. Identification of an activator protein required for the induction of fruA, a gene essential for fruiting body development in Myxococcus xanthus. Proc Natl Acad Sci USA 2003; 100:8782–8787.PubMedCrossRefGoogle Scholar
  23. 23.
    Ogawa M, Fujitani S, Mao X et al. FruA, a putative transcriptional factor essential for the development of Myxococcus xanthus. Mol Microbiol 1996; 22:757–767.PubMedCrossRefGoogle Scholar
  24. 24.
    Horiuchi T, Taoka M, Isobe T et al. Role of fruA and csgA in gene expression during development of Myxococcus xanthus: Analysis by two-dimensional gel electrophoresis. J Biol Chem 2002; 277:26753–60.PubMedCrossRefGoogle Scholar
  25. 25.
    Ellehauge E, Nørregaard-Madsen M, Søgaard-Andersen L. The FruA signal transduction protein provides a checkpoint for the temporal co-ordination of intercellular signals in Myxococcus xanthus development. Mol Microbiol 1998; 30:807–817.PubMedCrossRefGoogle Scholar
  26. 26.
    Inouye M, Inouye S, Zusman DR. Biosynthesis and self-assembly of protein S, a development-specific protein of Myxococcus xanthus. Proc Natl Acad Sci USA 1979; 76:209–213.PubMedCrossRefGoogle Scholar
  27. 27.
    Horiuchi T, Akiyama T, Inouye S et al. Analysis of dofA, a fruA-dependent developmental gene and its homologue, dofB, in Myxococcus xanthus. J Bacteriol 2002; 184:6803–6810.PubMedCrossRefGoogle Scholar
  28. 28.
    Inouye M, Inouye S, Zusman DR. Gene expression during development of Myxococcus xanthus: pattern of protein synthesis. Dev Biol 1979; 68:579–591.PubMedCrossRefGoogle Scholar
  29. 29.
    Søgaard-Andersen L, Kaiser D. C factor, a cell-surface-associated intercellular signaling protein, stimulates the Frz signal transduction system in Myxococcus xanthus. Proc Natl Acad Sci USA 1996; 93:2675–2679.PubMedCrossRefGoogle Scholar
  30. 30.
    McCleary WR, McBride MJ, Zusman DR. Developmental sensory transduction in Myxococcus xanthus involves methylation and demethylation of FrzCD. J Bacteriol 1990; 172:4877–4887.PubMedGoogle Scholar
  31. 31.
    Ward MJ, Zusman DR. Motility in Myxococcus xanthus and its role in developmental aggregation. Curr Opin Microbiol 1999; 2:624–629.PubMedCrossRefGoogle Scholar
  32. 32.
    Thony-Meyer L, Kaiser D. devRS, an autoregulated and essential genetic locus for fruiting body development in Myxococcus xanthus. J Bacteriol 1993; 175:7450–7462.PubMedGoogle Scholar
  33. 33.
    Ueki T, Inouye S. Identification of a gene involved in polysaccharide export as a transcription target of FruA, an essential factor for Myxococcus xanthus development. J Biol Chem 2005; 280:32279–32284.PubMedCrossRefGoogle Scholar
  34. 34.
    Nariya H, Inouye S. Identification of a protein Ser/Thr kinase cascade that regulates essential transcriptional activators in Myxococcus xanthus. Mol Microbiol 2005; 58:367–379.PubMedCrossRefGoogle Scholar
  35. 35.
    Nariya H, Inouye S. A protein Ser/Thr kinase cascade negatively regulates the DNA-binding activity of MrpC, a smaller form of which may be necessary for the Myxococcus xanthus development. Mol Microbiol 2006; 60:1205–1217.PubMedCrossRefGoogle Scholar
  36. 36.
    Korner H, Sofia HJ, Zumft WG. Phylogeny of the bacterial superfamily of Crp-Fnr transcription regulators: exploiting the metabolic spectrum by controlling alternative gene programs. FEMS Microbiol Rev 2003; 27:559–592.PubMedCrossRefGoogle Scholar
  37. 37.
    Buck M, Gallegos MT, Studholme DJ et al. The bacterial enhancer-dependent sigma(54) (sigma(N)) transcription factor. J Bacteriol 2000; 182:4129–4136.PubMedCrossRefGoogle Scholar
  38. 38.
    Hoover TR, Santero E, Porter S et al. The integration host factor stimulates interaction of RNA polymerase with NIFA, the transcriptional activator for nitrogen fixation operons. Cell 1990; 63:11–22.PubMedCrossRefGoogle Scholar
  39. 39.
    Muñoz-Dorado J, Inouye S, Inouye M. A gene encoding a protein serine/threonine kinase is required for normal development of M. xanthus, a gram-negative bacterium. Cell 1991; 67:996–1006.CrossRefGoogle Scholar
  40. 40.
    Udo H, Muñoz-Dorado J, Inouye M et al. Myxococcus xanthus, a gram-negative bacterium, contains a transmembrane protein serine/threonine kinase that blocks the secretion of β-lactamase by phosphorylation. Genes Dev 1995; 9:972–983.PubMedCrossRefGoogle Scholar
  41. 41.
    Zhang W, Inouye M, Inouye S. Reciprocal regulation of the differentiation of Myxococcus xanthus by Pkn5 and Pkn6, eukaryotic-like Ser/Thr protein kinases. Mol Microbiol 1996; 20:435–447.PubMedCrossRefGoogle Scholar
  42. 42.
    Hanlon WA, Inouye M, Inouye S. Pkn9, a Ser/Thr protein kinase involved in the development of Myxococcus xanthus. Mol Microbiol 1997; 23:459–471.PubMedCrossRefGoogle Scholar
  43. 43.
    Thomasson B, Link J, Stassinopoulos AG et al. MglA, a small GTPase, interacts with a tyrosine kinase to control type IV pili-mediated motility and development of Myxococcus xanthus. Mol Microbiol 2002; 46:1399–1413.PubMedCrossRefGoogle Scholar
  44. 44.
    Nariya H, Inouye S. Activation of 6-phosphofructokinase via phosphorylation by Pkn4, a protein Ser/Thr kinase of Myxococcus xanthus. Mol Microbiol 2002; 46:1353–1366.PubMedCrossRefGoogle Scholar
  45. 45.
    Nariya H, Inouye S. Factors that Modulate the Pkn4 Kinase Cascade in Myxococcus xanthus. J Mol Microbiol Biotechnol 2005; 9:147–153.PubMedCrossRefGoogle Scholar
  46. 46.
    Nariya H, Inouye S. Modulating factors for the Pkn4 kinase cascade in regulating 6-phosphofructokinase in Myxococcus xanthus. Mol Microbiol 2005; 56:1314–1328.PubMedCrossRefGoogle Scholar
  47. 47.
    Gill RE, Cull MG. Control of developmental gene expression by cell-to-cell interactions in Myxococcus xanthus. J Bacteriol 1986; 168:341–347.PubMedGoogle Scholar
  48. 48.
    Gill RE, Karlok M, Benton D. Myxococcus xanthus encodes an ATP-dependent protease which is required for developmental gene transcription and intercellular signaling. J Bacteriol 1993; 175:4538–4544.PubMedGoogle Scholar
  49. 49.
    Tojo N, Inouye S, Komano T. The lonD gene is homologous to the lon gene encoding an ATP-dependent protease and is essential for the development of Myxococcus xanthus. J Bacteriol 1993; 175:4545–4549.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  1. 1.Department of BiochemistryRobert Wood Johnson Medical SchoolPiscatawayUSA

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