Cell Cycle Control by the Master Regulator CtrA in

English version České info

In order to propagate, all living cells must ensure that their genetic material is faithfully copied and properly partitioned into the daughter cells before division. These coordinated processes of DNA replication and cell division are termed the “cell cycle” and are controlled by a complex network of regulatory proteins in all organisms. In the class Alphaproteobacteria, the regulation of the cell cycle is closely linked to cellular differentiation processes that are vital for survival in the environment. In these bacteria, the cell cycle regulator CtrA is thought to serve as the primary link between the coordination of the cell cycle and cellular differentiation. The alphaproteobacterium, Sinorhizobium meliloti, an important model symbiont of alfalfa plants, undergoes a striking cellular differentiation that is vital to the formation of an efficient symbiosis dedicated to the conversion of atmospheric nitrogen to biologically available organic nitrogen. However, the link between cellular differentiation and cell cycle control in S. meliloti has not been made. In this study, we showed that S. meliloti cells without CtrA are similar to the symbiotic form. By the identification of the genes whose expression is directly and indirectly controlled by CtrA, we found that CtrA regulates vital cell cycle processes, including DNA replication and cell division, but through different genetic pathways than in other alphaproteobacteria. We importantly show that the levels of CtrA protein are governed by an essential cell cycle regulated proteolysis, which may also be an important mode of CtrA down-regulation during symbiosis to drive cellular differentiation.

Vyšlo v časopise: Cell Cycle Control by the Master Regulator CtrA in. PLoS Genet 11(5): e32767. doi:10.1371/journal.pgen.1005232
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005232

Souhrn

Zdroje

1. Jones KM, Kobayashi H, Davies BW, Taga ME, Walker GC. How rhizobial symbionts invade plants: the Sinorhizobium-Medicago model. Nat Rev Microbiol. 2007;5 : 619–633. doi: 10.1038/nrmicro1705 17632573

2. Oke V, Long SR. Bacteroid formation in the Rhizobium-legume symbiosis. Curr Opin Microbiol. 1999;2 : 641–646. 10607628

3. Foucher F, Kondorosi E. Cell cycle regulation in the course of nodule organogenesis in Medicago. Plant Mol Biol. 2000;43 : 773–786. 11089876

4. Mergaert P, Uchiumi T, Alunni B, Evanno G, Cheron A, Catrice O, et al. Eukaryotic control on bacterial cell cycle and differentiation in the Rhizobium-legume symbiosis. Proc Natl Acad Sci U S A. 2006;103 : 5230–5235. doi: 10.1073/pnas.0600912103 16547129

5. Mergaert P, Nikovics K, Kelemen Z, Maunoury N, Vaubert D, Kondorosi A, et al. A novel family in Medicago truncatula consisting of more than 300 nodule-specific genes coding for small, secreted polypeptides with conserved cysteine motifs. Plant Physiol. 2003;132 : 161–173. doi: 10.1104/pp.102.018192 12746522

6. Alunni B, Kevei Z, Redondo-Nieto M, Kondorosi A, Mergaert P, Kondorosi E. Genomic organization and evolutionary insights on GRP and NCR genes, two large nodule-specific gene families in Medicago truncatula. Mol Plant-Microbe Interact MPMI. 2007;20 : 1138–1148. doi: 10.1094/MPMI-20-9-1138 17849716

7. Farkas A, Maróti G, Durgő H, Györgypál Z, Lima RM, Medzihradszky KF, et al. Medicago truncatula symbiotic peptide NCR247 contributes to bacteroid differentiation through multiple mechanisms. Proc Natl Acad Sci U S A. 2014;111 : 5183–5188. doi: 10.1073/pnas.1404169111 24706863

8. Gibson KE, Kobayashi H, Walker GC. Molecular determinants of a symbiotic chronic infection. Annu Rev Genet. 2008;42 : 413–441. doi: 10.1146/annurev.genet.42.110807.091427 18983260

9. Hallez R, Bellefontaine A-F, Letesson J-J, De Bolle X. Morphological and functional asymmetry in alpha-proteobacteria. Trends Microbiol. 2004;12 : 361–365. doi: 10.1016/j.tim.2004.06.002 15276611

10. Bird TH, MacKrell A. A CtrA homolog affects swarming motility and encystment in Rhodospirillum centenum. Arch Microbiol. 2011;193 : 451–459. doi: 10.1007/s00203-011-0676-y 21243338

11. Brilli M, Fondi M, Fani R, Mengoni A, Ferri L, Bazzicalupo M, et al. The diversity and evolution of cell cycle regulation in alpha-proteobacteria: a comparative genomic analysis. BMC Syst Biol. 2010;4 : 52. doi: 10.1186/1752-0509-4-52 20426835

12. Bellefontaine A-F, Pierreux CE, Mertens P, Vandenhaute J, Letesson J-J, De Bolle X. Plasticity of a transcriptional regulation network among alpha-proteobacteria is supported by the identification of CtrA targets in Brucella abortus. Mol Microbiol. 2002;43 : 945–960. 11929544

13. Greene SE, Brilli M, Biondi EG, Komeili A. Analysis of the CtrA pathway in Magnetospirillum reveals an ancestral role in motility in alphaproteobacteria. J Bacteriol. 2012;194 : 2973–2986. doi: 10.1128/JB.00170-12 22467786

14. Quon KC, Marczynski GT, Shapiro L. Cell cycle control by an essential bacterial two-component signal transduction protein. Cell. 1996;84 : 83–93. 8548829

15. Shapiro L. Differentiation in the Caulobacter cell cycle. Annu Rev Microbiol. 1976;30 : 377–407. doi: 10.1146/annurev.mi.30.100176.002113 185940

16. Skerker JM, Laub MT. Cell-cycle progression and the generation of asymmetry in Caulobacter crescentus. Nat Rev Microbiol. 2004;2 : 325–337. doi: 10.1038/nrmicro864 15031731

17. Quon KC, Yang B, Domian IJ, Shapiro L, Marczynski GT. Negative control of bacterial DNA replication by a cell cycle regulatory protein that binds at the chromosome origin. Proc Natl Acad Sci U S A. 1998;95 : 120–125. 9419339

18. Laub MT, Chen SL, Shapiro L, McAdams HH. Genes directly controlled by CtrA, a master regulator of the Caulobacter cell cycle. Proc Natl Acad Sci U S A. 2002;99 : 4632–4637. doi: 10.1073/pnas.062065699 11930012

19. Reisenauer A, Shapiro L. DNA methylation affects the cell cycle transcription of the CtrA global regulator in Caulobacter. EMBO J. 2002;21 : 4969–4977. 12234936

20. Holtzendorff J, Hung D, Brende P, Reisenauer A, Viollier PH, McAdams HH, et al. Oscillating global regulators control the genetic circuit driving a bacterial cell cycle. Science. 2004;304 : 983–987. doi: 10.1126/science.1095191 15087506

21. Ryan KR, Judd EM, Shapiro L. The CtrA response regulator essential for Caulobacter crescentus cell-cycle progression requires a bipartite degradation signal for temporally controlled proteolysis. J Mol Biol. 2002;324 : 443–455. 12445780

22. Domian IJ, Quon KC, Shapiro L. Cell type-specific phosphorylation and proteolysis of a transcriptional regulator controls the G1-to-S transition in a bacterial cell cycle. Cell. 1997;90 : 415–424. 9267022

23. Jacobs C, Domian IJ, Maddock JR, Shapiro L. Cell cycle-dependent polar localization of an essential bacterial histidine kinase that controls DNA replication and cell division. Cell. 1999;97 : 111–120. 10199407

24. Chen YE, Tsokos CG, Biondi EG, Perchuk BS, Laub MT. Dynamics of two Phosphorelays controlling cell cycle progression in Caulobacter crescentus. J Bacteriol. 2009;191 : 7417–7429. doi: 10.1128/JB.00992-09 19783630

25. Jacobs C, Ausmees N, Cordwell SJ, Shapiro L, Laub MT. Functions of the CckA histidine kinase in Caulobacter cell cycle control. Mol Microbiol. 2003;47 : 1279–1290. 12603734

26. Iniesta AA, McGrath PT, Reisenauer A, McAdams HH, Shapiro L. A phospho-signaling pathway controls the localization and activity of a protease complex critical for bacterial cell cycle progression. Proc Natl Acad Sci U S A. 2006;103 : 10935–10940. doi: 10.1073/pnas.0604554103 16829582

27. Biondi EG, Reisinger SJ, Skerker JM, Arif M, Perchuk BS, Ryan KR, et al. Regulation of the bacterial cell cycle by an integrated genetic circuit. Nature. 2006;444 : 899–904. doi: 10.1038/nature05321 17136100

28. Barnett MJ, Hung DY, Reisenauer A, Shapiro L, Long SR. A homolog of the CtrA cell cycle regulator is present and essential in Sinorhizobium meliloti. J Bacteriol. 2001;183 : 3204–3210. doi: 10.1128/JB.183.10.3204-3210.2001 11325950

29. Kobayashi H, De Nisco NJ, Chien P, Simmons LA, Walker GC. Sinorhizobium meliloti CpdR1 is critical for co-ordinating cell cycle progression and the symbiotic chronic infection. Mol Microbiol. 2009;73 : 586–600. doi: 10.1111/j.1365-2958.2009.06794.x 19602145

30. Gibson KE, Barnett MJ, Toman CJ, Long SR, Walker GC. The symbiosis regulator CbrA modulates a complex regulatory network affecting the flagellar apparatus and cell envelope proteins. J Bacteriol. 2007;189 : 3591–3602. doi: 10.1128/JB.01834-06 17237174

31. Gibson KE, Campbell GR, Lloret J, Walker GC. CbrA is a stationary-phase regulator of cell surface physiology and legume symbiosis in Sinorhizobium meliloti. J Bacteriol. 2006;188 : 4508–4521. doi: 10.1128/JB.01923-05 16740957

32. Sadowski C, Wilson D, Schallies K, Walker G, Gibson KE. The Sinorhizobium meliloti sensor histidine kinase CbrA contributes to free-living cell cycle regulation. Microbiol Read Engl. 2013; doi: 10.1099/mic.0.067504-0

33. Pini F, Frage B, Ferri L, De Nisco NJ, Mohapatra SS, Taddei L, et al. The DivJ, CbrA and PleC system controls DivK phosphorylation and symbiosis in Sinorhizobium meliloti. Mol Microbiol. 2013;90 : 54–71. doi: 10.1111/mmi.12347 23909720

34. Roux B, Rodde N, Jardinaud M-F, Timmers T, Sauviac L, Cottret L, et al. An integrated analysis of plant and bacterial gene expression in symbiotic root nodules using laser-capture microdissection coupled to RNA sequencing. Plant J Cell Mol Biol. 2014;77 : 817–837. doi: 10.1111/tpj.12442

35. Penterman J, Abo RP, De Nisco NJ, Arnold MFF, Longhi R, Zanda M, et al. Host plant peptides elicit a transcriptional response to control the Sinorhizobium meliloti cell cycle during symbiosis. Proc Natl Acad Sci U S A. 2014;111 : 3561–3566. doi: 10.1073/pnas.1400450111 24501120

36. Khan SR, Gaines J, Roop RM 2nd, Farrand SK. Broad-host-range expression vectors with tightly regulated promoters and their use to examine the influence of TraR and TraM expression on Ti plasmid quorum sensing. Appl Environ Microbiol. 2008;74 : 5053–5062. doi: 10.1128/AEM.01098-08 18606801

37. Cheng J, Sibley CD, Zaheer R, Finan TM. A Sinorhizobium meliloti minE mutant has an altered morphology and exhibits defects in legume symbiosis. Microbiol Read Engl. 2007;153 : 375–387. doi: 10.1099/mic.0.2006/001362-0

38. Johnson DS, Mortazavi A, Myers RM, Wold B. Genome-wide mapping of in vivo protein-DNA interactions. Science. 2007;316 : 1497–1502. doi: 10.1126/science.1141319 17540862

39. Schlüter J-P, Reinkensmeier J, Barnett MJ, Lang C, Krol E, Giegerich R, et al. Global mapping of transcription start sites and promoter motifs in the symbiotic α-proteobacterium Sinorhizobium meliloti 1021. BMC Genomics. 2013;14 : 156. doi: 10.1186/1471-2164-14-156 23497287

40. De Nisco NJ, Abo RP, Wu CM, Penterman J, Walker GC. Global analysis of cell cycle gene expression of the legume symbiont Sinorhizobium meliloti. Proc Natl Acad Sci U S A. 2014; doi: 10.1073/pnas.1400421111

41. Rotter C, Mühlbacher S, Salamon D, Schmitt R, Scharf B. Rem, a new transcriptional activator of motility and chemotaxis in Sinorhizobium meliloti. J Bacteriol. 2006;188 : 6932–6942. doi: 10.1128/JB.01902-05 16980496

42. Tan MH, Kozdon JB, Shen X, Shapiro L, McAdams HH. An essential transcription factor, SciP, enhances robustness of Caulobacter cell cycle regulation. Proc Natl Acad Sci U S A. 2010;107 : 18985–18990. doi: 10.1073/pnas.1014395107 20956288

43. Gora KG, Tsokos CG, Chen YE, Srinivasan BS, Perchuk BS, Laub MT. A cell-type-specific protein-protein interaction modulates transcriptional activity of a master regulator in Caulobacter crescentus. Mol Cell. 2010;39 : 455–467. doi: 10.1016/j.molcel.2010.06.024 20598601

44. Dehal PS, Joachimiak MP, Price MN, Bates JT, Baumohl JK, Chivian D, et al. MicrobesOnline: an integrated portal for comparative and functional genomics. Nucleic Acids Res. 2009; gkp919. doi: 10.1093/nar/gkp919

45. Shih Y-L, Zheng M. Spatial control of the cell division site by the Min system in Escherichia coli. Environ Microbiol. 2013;15 : 3229–3239. doi: 10.1111/1462-2920.12119 23574354

46. Hung DY, Shapiro L. A signal transduction protein cues proteolytic events critical to Caulobacter cell cycle progression. Proc Natl Acad Sci U S A. 2002;99 : 13160–13165. doi: 10.1073/pnas.202495099 12237413

47. Wortinger M, Sackett MJ, Brun YV. CtrA mediates a DNA replication checkpoint that prevents cell division in Caulobacter crescentus. EMBO J. 2000;19 : 4503–4512. doi: 10.1093/emboj/19.17.4503 10970844

48. Rothfield L, Taghbalout A, Shih Y-L. Spatial control of bacterial division-site placement. Nat Rev Microbiol. 2005;3 : 959–968. doi: 10.1038/nrmicro1290 16322744

49. Jenal U, Fuchs T. An essential protease involved in bacterial cell-cycle control. EMBO J. 1998;17 : 5658–5669. doi: 10.1093/emboj/17.19.5658 9755166

50. Fields AT, Navarrete CS, Zare AZ, Huang Z, Mostafavi M, Lewis JC, et al. The conserved polarity factor podJ1 impacts multiple cell envelope-associated functions in Sinorhizobium meliloti. Mol Microbiol. 2012;84 : 892–920. doi: 10.1111/j.1365-2958.2012.08064.x 22553970

51. McGrath PT, Iniesta AA, Ryan KR, Shapiro L, McAdams HH. A dynamically localized protease complex and a polar specificity factor control a cell cycle master regulator. Cell. 2006;124 : 535–547. doi: 10.1016/j.cell.2005.12.033 16469700

52. David M, Daveran ML, Batut J, Dedieu A, Domergue O, Ghai J, et al. Cascade regulation of nif gene expression in Rhizobium meliloti. Cell. 1988;54 : 671–683. 2842062

53. Galinier A, Garnerone AM, Reyrat JM, Kahn D, Batut J, Boistard P. Phosphorylation of the Rhizobium meliloti FixJ protein induces its binding to a compound regulatory region at the fixK promoter. J Biol Chem. 1994;269 : 23784–23789. 8089150

54. Monson EK, Ditta GS, Helinski DR. The oxygen sensor protein, FixL, of Rhizobium meliloti. Role of histidine residues in heme binding, phosphorylation, and signal transduction. J Biol Chem. 1995;270 : 5243–5250. 7890634

55. Gilles-Gonzalez MA, Ditta GS, Helinski DR. A haemoprotein with kinase activity encoded by the oxygen sensor of Rhizobium meliloti. Nature. 1991;350 : 170–172. doi: 10.1038/350170a0 1848683

56. Tiricz H, Szucs A, Farkas A, Pap B, Lima RM, Maróti G, et al. Antimicrobial nodule-specific cysteine-rich peptides induce membrane depolarization-associated changes in the transcriptome of Sinorhizobium meliloti. Appl Environ Microbiol. 2013;79 : 6737–6746. doi: 10.1128/AEM.01791-13 23995935

57. Sambrook JJ, Russell DDW. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press; 2001.

58. Beringer JE. R factor transfer in Rhizobium leguminosarum. J Gen Microbiol. 1974;84 : 188–198. 4612098

59. Simon R, Priefer U, Pühler A. A Broad Host Range Mobilization System for In Vivo Genetic Engineering: Transposon Mutagenesis in Gram Negative Bacteria. Nat Biotechnol. 1983;1 : 784–791. doi: 10.1038/nbt1183-784

60. Roberts RC, Toochinda C, Avedissian M, Baldini RL, Gomes SL, Shapiro L. Identification of a Caulobacter crescentus operon encoding hrcA, involved in negatively regulating heat-inducible transcription, and the chaperone gene grpE. J Bacteriol. 1996;178 : 1829–1841. 8606155

61. Alley MR, Gomes SL, Alexander W, Shapiro L. Genetic analysis of a temporally transcribed chemotaxis gene cluster in Caulobacter crescentus. Genetics. 1991;129 : 333–341. 1660425

62. Ferri L, Gori A, Biondi EG, Mengoni A, Bazzicalupo M. Plasmid electroporation of Sinorhizobium strains: The role of the restriction gene hsdR in type strain Rm1021. Plasmid. 2010;63 : 128–135. doi: 10.1016/j.plasmid.2010.01.001 20097223

63. Finan TM, Hartweig E, LeMieux K, Bergman K, Walker GC, Signer ER. General transduction in Rhizobium meliloti. J Bacteriol. 1984;159 : 120–124. 6330024

64. Fioravanti A, Fumeaux C, Mohapatra SS, Bompard C, Brilli M, Frandi A, et al. DNA Binding of the Cell Cycle Transcriptional Regulator GcrA Depends on N6-Adenosine Methylation in Caulobacter crescentus and Other Alphaproteobacteria. PLoS Genet. 2013;9: e1003541. doi: 10.1371/journal.pgen.1003541 23737758

65. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9 : 671–675. 22930834

66. Smyth GK. limma: Linear Models for Microarray Data. In: Gentleman R, Carey VJ, Huber W, Irizarry RA, Dudoit S, editors. Bioinformatics and Computational Biology Solutions Using R and Bioconductor. Springer New York; 2005. pp. 397–420. Available: http://link.springer.com/chapter/10.1007/0-387-29362-0_23

67. Smyth GK. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol. 2004;3: Article3. doi: 10.2202/1544-6115.1027 16646809

68. Edgar R, Domrachev M, Lash AE. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 2002;30 : 207–210. doi: 10.1093/nar/30.1.207 11752295

69. Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, et al. NCBI GEO: archive for functional genomics data sets—update. Nucleic Acids Res. 2013;41: D991–D995. doi: 10.1093/nar/gks1193 23193258

70. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods San Diego Calif. 2001;25 : 402–408. doi: 10.1006/meth.2001.1262 11846609

71. Krol E, Becker A. Global transcriptional analysis of the phosphate starvation response in Sinorhizobium meliloti strains 1021 and 2011. Mol Genet Genomics MGG. 2004;272 : 1–17. doi: 10.1007/s00438-004-1030-8

72. Domian IJ, Reisenauer A, Shapiro L. Feedback control of a master bacterial cell-cycle regulator. Proc Natl Acad Sci U S A. 1999;96 : 6648–6653. 10359766