Key Points
-
Cellular differentiation and asymmetric cell division is an integral part of the cell cycle in the bacterium Caulobacter crescentus.
-
The timing of differentiation and cell-cycle events are tightly controlled by the regulated synthesis, activity, stability and localization of many proteins.
-
The CtrA transcriptional regulator controls the execution of several cell-cycle and differentiation events.
-
Cell-cycle-specific degradation and phosphorylation control the activity of CtrA during the cell cycle.
-
Kinases that are involved in CtrA phosphorylation dynamically localize to specific intracellular sites, which indicates that spatial cues might have a role in regulating CtrA activation.
-
The timing of DNA replication and the organization of the chromosome within the cell are coordinated with cell-cycle progression. Specific regions of the chromosome rapidly and dynamically move to specific intracellular sites during DNA replication.
-
DNA replication itself and the organization and compaction of the newly replicated DNA contribute to chromosome segregation.
-
An integrated approach is being used to understand the control of cell-cycle progression through the coordination of gene transcription, protein availability, activation by phosphorylation and intracellular localization.
Abstract
A cellular differentiation programme that culminates in an asymmetric cell division is an integral part of the cell cycle in the bacterium Caulobacter crescentus. Recent work has uncovered mechanisms that ensure the execution of many events at different times during the cell cycle and at specific places in the cell. Surprisingly, in this one-micron bacterial cell, the dynamic spatial disposition of regulatory proteins, structural proteins and specific regions of the chromosome are important components of both cell-cycle progression and the generation of daughter cells with different cell fates.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Horvitz, H. R. & Herskowitz, I. Mechanisms of asymmetric cell division: two Bs or not two Bs, that is the question. Cell 68, 237?255 (1992).
Rudner, D. Z. & Losick, R. Morphological coupling in development. Lessons from prokaryotes. Dev. Cell 1, 733?742 (2001).
Takizawa, P. A., Sil, A., Swedlow, J. R., Herskowitz, I. & Vale, R. D. Actin-dependent localization of an RNA encoding a cell-fate determinant in yeast. Nature 389, 90?93 (1997).
Long, R. M. et al. Mating type switching in yeast controlled by asymmetric localization of ASH1 mRNA. Science 277, 383?387 (1997).
Shapiro, L. & Losick, R. Dynamic spatial regulation in the bacterial cell. Cell 100, 89?98 (2000).
Jenal, U., Stephens, C. & Shapiro, L. Regulation of asymmetry and polarity during the Caulobacter cell cycle. Adv. Enzymol. Relat. Areas Mol. Biol. 71, 1?39 (1995).
Hung, D., McAdams, H. & Shapiro, L. in Prokaryotic Development (eds Brun, Y. V. & Shimkets, L. J.) 361?377 (ASM Press, Washington D. C., 2000).
Nierman, W. C. et al. Complete genome sequence of Caulobacter crescentus. Proc. Natl Acad. Sci. USA 98, 4136?4141 (2001).
Laub, M. T., McAdams, H. H., Feldblyum, T., Fraser, C. M. & Shapiro, L. Global analysis of the genetic network controlling a bacterial cell cycle. Science 290, 2144?2148 (2000).Microarray analysis of mRNA abundance patterns during the Caulobacter cell cycle showed that a surprisingly large number of genes are differentially transcribed at the time when their protein products are required for a specific function.
Grunenfelder, B. et al. Proteomic analysis of the bacterial cell cycle. Proc. Natl Acad. Sci. USA 98, 4681?4686 (2001).
Ohta, N., Chen, L. S., Swanson, E. & Newton, A. Transcriptional regulation of a periodically controlled flagellar gene operon in Caulobacter crescentus. J. Mol. Biol. 186, 107?115 (1985).
Champer, R., Dingwall, A. & Shapiro, L. Cascade regulation of Caulobacter flagellar and chemotaxis genes. J. Mol. Biol. 194, 71?80 (1987).
Skerker, J. M. & Shapiro, L. Identification and cell cycle control of a novel pilus system in Caulobacter crescentus. EMBO J. 19, 3223?3234 (2000).
Quon, K. C., Marczynski, G. T. & Shapiro, L. Cell cycle control by an essential bacterial two-component signal transduction protein. Cell 84, 83?93 (1996).The discovery of the CtrA cell-cycle regulator.
Wu, J. & Newton, A. Regulation of the Caulobacter flagellar gene hierarchy; not just for motility. Mol. Microbiol. 24, 233?239 (1997).
Gober, J. W. & England, J. C. in Prokaryotic Development (eds Brun, Y. V. & Shimkets, L. J.) 319?339 (ASM Press, Washington D. C., 2000).
Wu, J., Ohta, N. & Newton, A. An essential, multicomponent signal transduction pathway required for cell cycle regulation in Caulobacter. Proc. Natl Acad. Sci. USA 95, 1443?1448 (1998).
Ramakrishnan, G. & Newton, A. FlbD of Caulobacter crescentus is a homologue of the NtrC (NRI) protein and activates sigma 54-dependent flagellar gene promoters. Proc. Natl Acad. Sci. USA 87, 2369?2373 (1990).
Brun, Y. V. & Shapiro, L. A temporally controlled σ-factor is required for polar morphogenesis and normal cell division in Caulobacter. Genes Dev. 6, 2395?2408 (1992).
Alley, M. R., Gomes, S. L., Alexander, W. & Shapiro, L. Genetic analysis of a temporally transcribed chemotaxis gene cluster in Caulobacter crescentus. Genetics 129, 333?341 (1991).
Alley, M. R., Maddock, J. R. & Shapiro, L. Polar localization of a bacterial chemoreceptor. Genes Dev. 6, 825?836 (1992).The first demonstration of localization of a signalling protein to a specific intracellular site in a prokaryote.
Jones, S. E., Ferguson, N. L. & Alley, M. R. New members of the ctrA regulon: the major chemotaxis operon in Caulobacter is CtrA dependent. Microbiology 147, 949?958 (2001).
Kelly, A. J., Sackett, M. J., Din, N., Quardokus, E. & Brun, Y. V. Cell cycle-dependent transcriptional and proteolytic regulation of FtsZ in Caulobacter. Genes Dev. 12, 880?893 (1998).
Quardokus, E., Din, N. & Brun, Y. V. Cell cycle regulation and cell type-specific localization of the FtsZ division initiation protein in Caulobacter. Proc. Natl Acad. Sci. USA 93, 6314?6319 (1996).
Wortinger, M., Sackett, M. J. & Brun, Y. V. CtrA mediates a DNA replication checkpoint that prevents cell division in Caulobacter crescentus. EMBO J. 19, 4503?4512 (2000).
Sackett, M. J., Kelly, A. J. & Brun, Y. V. Ordered expression of ftsQA and ftsZ during the Caulobacter crescentus cell cycle. Mol. Microbiol. 28, 421?434 (1998).
Brun, Y. V. Global analysis of a bacterial cell cycle: tracking down necessary functions and their regulators. Trends Microbiol. 9, 405?407 (2001).
Quon, K. C., Yang, B., Domian, I. J., Shapiro, L. & Marczynski, G. T. Negative control of bacterial DNA replication by a cell cycle regulatory protein that binds at the chromosome origin. Proc. Natl Acad. Sci. USA 95, 120?125 (1998).
Domian, I. J., Quon, K. C. & Shapiro, L. Cell type-specific phosphorylation and proteolysis of a transcriptional regulator controls the G1-to-S transition in a bacterial cell cycle. Cell 90, 415?424 (1997).This paper provides evidence that both phosphorylation and proteolysis control the activity of the CtrA cell-cycle regulator in a cell-cycle-dependent manner.
Stephens, C., Reisenauer, A., Wright, R. & Shapiro, L. A cell cycle-regulated bacterial DNA methyltransferase is essential for viability. Proc. Natl Acad. Sci. USA 93, 1210?1214 (1996).
Reisenauer, A., Quon, K. & Shapiro, L. The CtrA response regulator mediates temporal control of gene expression during the Caulobacter cell cycle. J. Bacteriol. 181, 2430?2439 (1999).
Wright, R., Stephens, C., Zweiger, G., Shapiro, L. & Alley, M. R. Caulobacter Lon protease has a critical role in cell-cycle control of DNA methylation. Genes Dev. 10, 1532?1542 (1996).
Marczynski, G. T. Chromosome methylation and measurement of faithful, once and only once per cell cycle chromosome replication in Caulobacter crescentus. J. Bacteriol. 181, 1984?1993 (1999).
Reisenauer, A., Kahng, L. S., McCollum, S. & Shapiro, L. Bacterial DNA methylation: a cell cycle regulator? J. Bacteriol. 181, 5135?5139 (1999).
Jenal, U. & Fuchs, T. An essential protease involved in bacterial cell-cycle control. EMBO J. 17, 5658?5669 (1998).
Domian, I. J., Reisenauer, A. & Shapiro, L. Feedback control of a master bacterial cell-cycle regulator. Proc. Natl Acad. Sci. USA 96, 6648?6653 (1999).
Jacobs, C., Domian, I. J., Maddock, J. R. & Shapiro, L. Cell cycle-dependent polar localization of an essential bacterial histidine kinase that controls DNA replication and cell division. Cell 97, 111?120 (1999).This work describes how dynamic intracellular localization of a signalling protein might restrict its activity to certain periods of the cell cycle.
Wu, J., Ohta, N., Zhao, J. L. & Newton, A. A novel bacterial tyrosine kinase essential for cell division and differentiation. Proc. Natl Acad. Sci. USA 96, 13068?13073 (1999).
Osley, M. A. & Newton, A. Temporal control of the cell cycle in Caulobacter crescentus: roles of DNA chain elongation and completion. J. Mol. Biol. 138, 109?128 (1980).
Sommer, J. M. & Newton, A. Pseudoreversion analysis indicates a direct role of cell division genes in polar morphogenesis and differentiation in Caulobacter crescentus. Genetics 129, 623?630 (1991).
Wang, S. P., Sharma, P. L., Schoenlein, P. V. & Ely, B. A histidine protein kinase is involved in polar organelle development in Caulobacter crescentus. Proc. Natl Acad. Sci. USA 90, 630?634 (1993).
Hecht, G. B., Lane, T., Ohta, N., Sommer, J. M. & Newton, A. An essential single domain response regulator required for normal cell division and differentiation in Caulobacter crescentus EMBO J. 14, 3915?3924 (1995).
Wheeler, R. T. & Shapiro, L. Differential localization of two histidine kinases controlling bacterial cell differentiation. Mol. Cell 4, 683?694 (1999).
Jacobs, C., Hung, D. & Shapiro, L. Dynamic localization of a cytoplasmic signal transduction response regulator controls morphogenesis during the Caulobacter cell cycle. Proc. Natl Acad. Sci. USA 98, 4095?4100 (2001).
Elowitz, M. B., Surette, M. G., Wolf, P. E., Stock, J. B. & Leibler, S. Protein mobility in the cytoplasm of Escherichia coli. J. Bacteriol. 181, 197?203 (1999).
Jensen, R. B. & Shapiro, L. Chromosome segregation during the prokaryotic cell division cycle. Curr. Opin. Cell. Biol. 11, 726?731 (1999).
Degnen, S. T. & Newton, A. Chromosome replication during development in Caulobacter crescentus. J. Mol. Biol. 64, 671?680 (1972).
Dingwall, A. & Shapiro, L. Rate, origin, and bidirectionality of Caulobacter chromosome replication as determined by pulsed-field gel electrophoresis. Proc. Natl Acad. Sci. USA 86, 119?123 (1989).
Marczynski, G. T., Dingwall, A. & Shapiro, L. Plasmid and chromosomal DNA replication and partitioning during the Caulobacter crescentus cell cycle. J. Mol. Biol. 212, 709?722 (1990).
Marczynski, G. T. & Shapiro, L. Cell-cycle control of a cloned chromosomal origin of replication from Caulobacter crescentus. J. Mol. Biol. 226, 959?977 (1992).
Brassinga, A. K. & Marczynski, G. T. Replication intermediate analysis confirms that chromosomal replication origin initiates from an unusual intergenic region in Caulobacter crescentus. Nucleic Acids Res. 29, 4441?4451 (2001).
Degnen, S. T. & Newton, A. Dependence of cell division on the completion of chromosome replication in Caulobacter. J. Bacteriol. 110, 852?856 (1972).
Siam, R. & Marczynski, G. T. Cell cycle regulator phosphorylation stimulates two distinct modes of binding at a chromosome replication origin. EMBO J. 19, 1138?1147 (2000).
Marczynski, G. T., Lentine, K. & Shapiro, L. A developmentally regulated chromosomal origin of replication uses essential transcription elements. Genes Dev. 9, 1543?1557 (1995).
Gorbatyuk, B. & Marczynski, G. T. Physiological consequences of blocked Caulobacter crescentus dnaA expression, an essential DNA replication gene. Mol. Microbiol. 40, 485?497 (2001).
Zweiger, G. & Shapiro, L. Expression of Caulobacter dnaA as a function of the cell cycle. J. Bacteriol. 176, 401?408 (1994).
Gomes, S. L., Gober, J. W. & Shapiro, L. Expression of the Caulobacter heat shock gene dnaK is developmentally controlled during growth at normal temperatures. J. Bacteriol. 172, 3051?3059 (1990).
Roberts, R. C. & Shapiro, L. Transcription of genes encoding DNA replication proteins is coincident with cell cycle control of DNA replication in Caulobacter crescentus. J. Bacteriol. 179, 2319?2330 (1997).
Winzeler, E. & Shapiro, L. A novel promoter motif for Caulobacter cell cycle-controlled DNA replication genes. J. Mol. Biol. 264, 412?425 (1996).
Keiler, K. C. & Shapiro, L. Conserved promoter motif is required for cell cycle timing of dnaX transcription in Caulobacter. J. Bacteriol. 183, 4860?4865 (2001).
Pettijohn, D. E. in Escherichia coli and Salmonella: Cellular and Molecular Biology, Second Edition (eds Niedhardt, F. C. et al.) 158?166 (ASM Press, Washington D. C., 1996).
Kavenoff, R. & Ryder, O. A. Electron microscopy of membrane-associated folded chromosomes of Escherichia coli. Chromosoma 55, 13?25 (1976).
Kornberg, A. & Baker, T. A. DNA replication (Freeman, New York, 1992).
Lemon, K. P. & Grossman, A. D. Localization of bacterial DNA polymerase: evidence for a factory model of replication. Science 282, 1516?1519 (1998).This study provides evidence that DNA replication in B. subtilis takes place at an immobile factory located mid-cell, and implies that it is DNA and not the DNA polymerase that moves during the replication process.
Lemon, K. P. & Grossman, A. D. Movement of replicating DNA through a stationary replisome. Mol. Cell 6, 1321?1330 (2000).
Jensen, R. B., Wang, S. C. & Shapiro, L. A moving DNA replication factory in Caulobacter crescentus. EMBO J. 20, 4952?4963 (2001).
Gordon, G. S. et al. Chromosome and low copy plasmid segregation in E. coli: visual evidence for distinct mechanisms. Cell 90, 1113?1121 (1997).
Webb, C. D. et al. Use of time-lapse microscopy to visualize rapid movement of the replication origin region of the chromosome during the cell cycle in Bacillus subtilis. Mol. Microbiol. 28, 883?892 (1998).
Jensen, R. B. & Shapiro, L. The Caulobacter crescentus smc gene is required for cell cycle progression and chromosome segregation. Proc. Natl Acad. Sci. USA 96, 10661?10666 (1999).References 67?69 show rapid and specific movement of the origin-proximal region of the chromosome during the bacterial cell cycle.
Vologodskii, A. V. & Cozzarelli, N. R. Conformational and thermodynamic properties of supercoiled DNA. Annu. Rev. Biophys. Biomol. Struct. 23, 609?643 (1994).
Holmes, V. F. & Cozzarelli, N. R. Closing the ring: links between SMC proteins and chromosome partitioning, condensation, and supercoiling. Proc. Natl Acad. Sci. USA 97, 1322?1324 (2000).
Britton, R. A., Lin, D. C. & Grossman, A. D. Characterization of a prokaryotic SMC protein involved in chromosome partitioning. Genes Dev. 12, 1254?1259 (1998).
Moriya, S. et al. A Bacillus subtilis gene-encoding protein homologous to eukaryotic SMC motor protein is necessary for chromosome partition. Mol. Microbiol. 29, 179?187 (1998).
Cobbe, N. & Heck, M. M. Review: SMCs in the world of chromosome biology?from prokaryotes to higher eukaryotes. J. Struct. Biol. 129, 123?143 (2000).
Graumann, P. L. SMC proteins in bacteria: condensation motors for chromosome segregation? Biochimie 83, 53?59 (2001).
Niki, H., Jaffe, A., Imamura, R., Ogura, T. & Hiraga, S. The new gene mukB codes for a 177-kd protein with coiled-coil domains involved in chromosome partitioning of E. coli. EMBO J. 10, 183?193 (1991).
Mohl, D. A. & Gober, J. W. Cell cycle-dependent polar localization of chromosome partitioning proteins in Caulobacter crescentus. Cell 88, 675?684 (1997).
Ireton, K., Gunther, N. W. T. & Grossman, A. D. spo0J is required for normal chromosome segregation as well as the initiation of sporulation in Bacillus subtilis. J. Bacteriol. 176, 5320?5329 (1994).
Sharpe, M. E. & Errington, J. The Bacillus subtilis soj-spo0J locus is required for a centromere-like function involved in prespore chromosome partitioning. Mol. Microbiol. 21, 501?509 (1996).
Hoch, J. A. Two-component and phosphorelay signal transduction. Curr. Opin. Microbiol. 3, 165?170 (2000).
Stallmeyer, M. J., Hahnenberger, K. M., Sosinsky, G. E., Shapiro, L. & DeRosier, D. J. Image reconstruction of the flagellar basal body of Caulobacter crescentus. J. Mol. Biol. 205, 511?518 (1989).
Wagenknecht, T., DeRosier, D., Shapiro, L. & Weissborn, A. Three-dimensional reconstruction of the flagellar hook from Caulobacter crescentus. J. Mol. Biol. 151, 439?465 (1981).
Trachtenberg, S. & DeRosier, D. J. Three-dimensional reconstruction of the flagellar filament of Caulobacter crescentus. A flagellin lacking the outer domain and its amino acid sequence lacking an internal segment. J. Mol. Biol. 202, 787?808 (1988).
Mangan, E. K., Bartamian, M. & Gober, J. W. A mutation that uncouples flagellum assembly from transcription alters the temporal pattern of flagellar gene expression in Caulobacter crescentus. J. Bacteriol. 177, 3176?3184 (1995).
Muir, R. E., O'Brien, T. M. & Gober, J. W. The Caulobacter crescentus flagellar gene, fliX, encodes a novel trans-acting factor that couples flagellar assembly to transcription. Mol. Microbiol. 39, 1623?1637 (2001).
Wingrove, J. A., Mangan, E. K. & Gober, J. W. Spatial and temporal phosphorylation of a transcriptional activator regulates pole-specific gene expression in Caulobacter. Genes Dev. 7, 1979?1992 (1993).
Anderson, D. K. & Newton, A. Posttranscriptional regulation of Caulobacter flagellin genes by a late flagellum assembly checkpoint. J. Bacteriol. 179, 2281?2288 (1997).
Quardokus, E. M., Din, N. & Brun, Y. V. Cell cycle and positional constraints on FtsZ localization and the initiation of cell division in Caulobacter crescentus. Mol. Microbiol. 39, 949?959 (2001).
Margolin, W. Themes and variations in prokaryotic cell division. FEMS Microbiol. Rev. 24, 531?548 (2000).
Acknowledgements
Portions of the work described here were supported by grants from the National Institutes of Health. R.B.J. was supported by fellowships from EMBO and the Carlsberg Foundation.
Author information
Authors and Affiliations
Corresponding author
Glossary
- FLAGELLUM
-
The cell motility apparatus in swimming bacteria.
- PILI
-
Long, thin organelles that are present on the outer surface of some bacteria, and are formed by polymerization of the pilin protein.
- ORIGIN OF DNA REPLICATION
-
The specific region in the chromosome in which initiation of DNA replication takes place.
- SECRETION APPARATUS
-
The machinery that transports proteins through the cytoplasmic membrane and the cell wall.
- HEMI-METHYLATED
-
One DNA strand is methylated, whereas the other is unmethylated.
- DNA METHYLTRANSFERASE
-
An enzyme that transfers methyl-groups from S-adenosylmethionine to specific adenines or cytosines in DNA.
- LON PROTEASE
-
A bacterial ATP-dependent protease.
- PHOSPHORELAY PATHWAYS
-
Complex pathways in which phosphoryl groups are transferred through several signal-transduction proteins before reaching the target protein.
- DNA POLYMERASE III
-
The enzyme that replicates the bulk of the chromosomal DNA in bacteria.
- TOPOISOMERASES
-
Enzymes that change DNA supercoiling by inserting or removing superhelical twists.
- HELICASES
-
Enzymes that separate the two DNA strands in a double helix, which results in the formation of regions of single-stranded DNA.
- REPLISOME
-
A multi-protein complex that contains all the enzymes that are required for DNA replication.
- SUPERCOILING
-
The under- or over-twisting of the DNA superhelix, which results in the DNA being drawn in on itself.
Rights and permissions
About this article
Cite this article
Jensen, R., Wang, S. & Shapiro, L. Dynamic localization of proteins and DNA during a bacterial cell cycle. Nat Rev Mol Cell Biol 3, 167–176 (2002). https://doi.org/10.1038/nrm758
Issue Date:
DOI: https://doi.org/10.1038/nrm758
This article is cited by
-
Involvement of organic acids and amino acids in ameliorating Ni(II) toxicity induced cell cycle dysregulation in Caulobacter crescentus: a metabolomics analysis
Applied Microbiology and Biotechnology (2018)
-
Alternatives to binary fission in bacteria
Nature Reviews Microbiology (2005)
-
Organ grinder not monkey?
Nature Reviews Genetics (2003)
-
Dynamic proteins and a cytoskeleton in bacteria
Nature Cell Biology (2003)