Potential Role of a Bistable Histidine Kinase Switch in the Asymmetric Division Cycle of Caulobacter crescentus

The free-living aquatic bacterium, Caulobacter crescentus, exhibits two different morphologies during its life cycle. The morphological change from swarmer cell to stalked cell is a result of changes of function of two bi-functional histidine kinases, PleC and CckA. Here, we describe a detailed molecular mechanism by which the function of PleC changes between phosphatase and kinase state. By mathematical modeling of our proposed molecular interactions, we derive conditions under which PleC, CckA and its response regulators exhibit bistable behavior, thus providing a scenario for robust switching between swarmer and stalked states. Our simulations are in reasonable agreement with in vitro and in vivo experimental observations of wild type and mutant phenotypes. According to our model, the kinase form of PleC is essential for the swarmer-to-stalked transition and to prevent premature development of the swarmer pole. Based on our results, we reconcile some published experimental observations and suggest novel mutants to test our predictions.

[1]  A. Newton,et al.  An essential, multicomponent signal transduction pathway required for cell cycle regulation in Caulobacter. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Lucy Shapiro,et al.  Genes directly controlled by CtrA, a master regulator of the Caulobacter cell cycle , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[3]  S. Crosson,et al.  ppGpp and Polyphosphate Modulate Cell Cycle Progression in Caulobacter crescentus , 2011, Journal of bacteriology.

[4]  L. Shapiro,et al.  Microbial asymmetric cell division: localization of cell fate determinants. , 1998, Current opinion in genetics & development.

[5]  Michael T. Laub,et al.  Dynamics of Two Phosphorelays Controlling Cell Cycle Progression in Caulobacter crescentus , 2009, Journal of bacteriology.

[6]  Patrick T McGrath,et al.  A phospho-signaling pathway controls the localization and activity of a protease complex critical for bacterial cell cycle progression. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[7]  John J. Tyson,et al.  Irreversible cell-cycle transitions are due to systems-level feedback , 2007, Nature Cell Biology.

[8]  John J. Tyson,et al.  Hysteresis drives cell-cycle transitions in Xenopus laevis egg extracts , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Nathan J Hillson,et al.  Cell pole–specific activation of a critical bacterial cell cycle kinase , 2010, Proceedings of the National Academy of Sciences.

[10]  A. Newton,et al.  An essential single domain response regulator required for normal cell division and differentiation in Caulobacter crescentus. , 1995, The EMBO journal.

[11]  Lucy Shapiro,et al.  Cell Cycle–Dependent Polar Localization of an Essential Bacterial Histidine Kinase that Controls DNA Replication and Cell Division , 1999, Cell.

[12]  A. Ninfa,et al.  Development of Genetic Circuitry Exhibiting Toggle Switch or Oscillatory Behavior in Escherichia coli , 2003, Cell.

[13]  L. Shapiro,et al.  The control of temporal and spatial organization during the Caulobacter cell cycle. , 1996, Current opinion in genetics & development.

[14]  L. Shapiro,et al.  Negative control of bacterial DNA replication by a cell cycle regulatory protein that binds at the chromosome origin. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Lucy Shapiro,et al.  A signal transduction protein cues proteolytic events critical to Caulobacter cell cycle progression , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Kerwyn Casey Huang,et al.  Interplay between the Localization and Kinetics of Phosphorylation in Flagellar Pole Development of the Bacterium Caulobacter crescentus , 2012, PLoS Comput. Biol..

[17]  A. Arkin,et al.  Stochastic kinetic analysis of developmental pathway bifurcation in phage lambda-infected Escherichia coli cells. , 1998, Genetics.

[18]  Balaji S. Srinivasan,et al.  A cell-type-specific protein-protein interaction modulates transcriptional activity of a master regulator in Caulobacter crescentus. , 2010, Molecular cell.

[19]  Stuart J Cordwell,et al.  Functions of the CckA histidine kinase in Caulobacter cell cycle control , 2003, Molecular microbiology.

[20]  Nathan J. Hillson,et al.  Polar Remodeling and Histidine Kinase Activation, Which Is Essential for Caulobacter Cell Cycle Progression, Are Dependent on DNA Replication Initiation , 2010, Journal of bacteriology.

[21]  Dan Siegal-Gaskins,et al.  Tightly regulated and heritable division control in single bacterial cells. , 2008, Biophysical journal.

[22]  John D. Hunter,et al.  Matplotlib: A 2D Graphics Environment , 2007, Computing in Science & Engineering.

[23]  Katherine C. Chen,et al.  Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. , 2003, Current opinion in cell biology.

[24]  Dylan T Burnette,et al.  Cytokinesis Monitoring during Development Rapid Pole-to-Pole Shuttling of a Signaling Protein by Localized Kinase and Phosphatase in Caulobacter , 2004, Cell.

[25]  Norbert F Scherer,et al.  Single-gene tuning of Caulobacter cell cycle period and noise, swarming motility, and surface adhesion , 2010, Molecular systems biology.

[26]  Michael T Laub,et al.  Spatial gradient of protein phosphorylation underlies replicative asymmetry in a bacterium , 2010, Proceedings of the National Academy of Sciences.

[27]  J. Collins,et al.  Construction of a genetic toggle switch in Escherichia coli , 2000, Nature.

[28]  Ellen M. Quardokus,et al.  Mutations in DivL and CckA Rescue a divJ Null Mutant of Caulobacter crescentus by Reducing the Activity of CtrA , 2006, Journal of bacteriology.

[29]  A. Newton,et al.  The Core Dimerization Domains of Histidine Kinases Contain Recognition Specificity for the Cognate Response Regulator , 2003, Journal of bacteriology.

[30]  Tae J. Lee,et al.  A bistable Rb–E2F switch underlies the restriction point , 2008, Nature Cell Biology.

[31]  J. Changeux.  Allostery and the Monod-Wyman-Changeux model after 50 years. , 2012, Annual review of biophysics.

[32]  John J. Tyson,et al.  Temporal Controls of the Asymmetric Cell Division Cycle in Caulobacter crescentus , 2009, PLoS Comput. Biol..

[33]  Yves V. Brun,et al.  Getting in the Loop: Regulation of Development in Caulobacter crescentus , 2010, Microbiology and Molecular Biology Reviews.

[34]  L. Shapiro,et al.  Dynamic localization of a cytoplasmic signal transduction response regulator controls morphogenesis during the Caulobacter cell cycle , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Patrick Goymer,et al.  Role of the GGDEF regulator PleD in polar development of Caulobacter crescentus , 2003, Molecular microbiology.

[36]  Lucy Shapiro,et al.  A bacterial control circuit integrates polar localization and proteolysis of key regulatory proteins with a phospho-signaling cascade , 2008, Proceedings of the National Academy of Sciences.

[37]  J Wu,et al.  A novel bacterial tyrosine kinase essential for cell division and differentiation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[38]  John J. Tyson,et al.  A Quantitative Study of the Division Cycle of Caulobacter crescentus Stalked Cells , 2007, PLoS Comput. Biol..

[39]  Michael T Laub,et al.  A dynamic complex of signaling proteins uses polar localization to regulate cell-fate asymmetry in Caulobacter crescentus. , 2011, Developmental cell.

[40]  H. Lam,et al.  The asymmetric spatial distribution of bacterial signal transduction proteins coordinates cell cycle events. , 2003, Developmental cell.

[41]  U. Jenal,et al.  Activation of the Diguanylate Cyclase PleD by Phosphorylation-mediated Dimerization* , 2007, Journal of Biological Chemistry.

[42]  L. Shapiro,et al.  Differential localization of two histidine kinases controlling bacterial cell differentiation. , 1999, Molecular cell.

[43]  R. Stewart,et al.  Protein histidine kinases: assembly of active sites and their regulation in signaling pathways. , 2010, Current opinion in microbiology.

[44]  E. G. Ninfa,et al.  A histidine protein kinase homologue required for regulation of bacterial cell division and differentiation. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[45]  P. Viollier,et al.  DivL Performs Critical Cell Cycle Functions in Caulobacter crescentus Independent of Kinase Activity , 2007, Journal of bacteriology.

[46]  Michael T. Laub,et al.  Regulation of the bacterial cell cycle by an integrated genetic circuit , 2006, Nature.