scholarly journals Analysis ofBrevundimonas subvibrioidesdevelopmental signaling systems reveals unexpected differences between phenotypes and c-di-GMP levels

2019 ◽  
Author(s):  
Lauryn Sperling ◽  
Volkhard Kaever ◽  
Patrick D. Curtis
Keyword(s):  
Cell Cycle ◽  
Caulobacter Crescentus ◽  
Diguanylate Cyclase ◽  
Critical Function ◽  
Minimal Impact ◽  
Phenotypic Differences ◽  
Signaling Systems ◽  
Physiological Processes ◽  
Suppressor Mutations ◽  
Polar Development

AbstractThe DivJ-DivK-PleC signaling system ofCaulobacter crescentusis a signaling network that regulates polar development and the cell cycle. This system is conserved in related bacteria, including the sister genusBrevundimonas. Previous studies had shown unexpected phenotypic differences between theC. crescentus divKmutant and the analogous mutant ofBrevundimonas subvibrioides, but further characterization was not performed. Here, phenotypic assays analyzing motility, adhesion, and pilus production (the latter characterized by a newly discovered bacteriophage) revealed thatdivJandpleCmutants have mostly similar phenotypes as theirC. crescentushomologs, butdivKmutants maintain largely opposite phenotypes than expected. Suppressor mutations of theB. subvibrioides divKmotility defect were involved in cyclic-di-GMP (c-di-GMP) signaling, including the diguanylate cyclasedgcB, andcleDwhich is hypothesized to affect flagellar function in a c-di-GMP dependent fashion. However, the screen did not identify the diguanylate cyclasepleD.Disruption ofpleDinB. subvibrioidescaused hypermotility in wild-type, but not in thedivKbackground. Analysis of c-di-GMP levels in these strains revealed incongruities between c-di-GMP levels and displayed phenotypes with a notable result that suppressor mutations altered phenotypes but had little impact on c-di-GMP levels in thedivKbackground. Conversely, when c-di-GMP levels were artificially manipulated, alterations of c-di-GMP levels in thedivKstrain had minimal impact on phenotypes. These results suggest that DivK performs a critical function in the integration of c-di-GMP signaling into theB. subvibrioidescell cycle.ImportanceCyclic-di-GMP signaling is one of the most broadly conserved signaling systems in bacteria, but there is little understanding of how this system directly affects the physiology of the organism. InC. crescentus, c-di-GMP has been integrated into the developmental cell cycle, but there is increasing evidence that environmental factors can impact this system as well. The research presented here suggests that developmental signaling could impact physiological Processes in c-di-GMP dependent and independent ways. This hints that the integration of these signaling networks could be more complex than previously hypothesized, which could have a bearing on the larger field of c-di-GMP signaling. In addition, this work further examines how much models developed in one organism can be extrapolated to related organisms.

scholarly journals Analysis of Brevundimonas subvibrioides Developmental Signaling Systems Reveals Inconsistencies between Phenotypes and c-di-GMP Levels

2019 ◽  
Vol 201 (20) ◽  
Author(s):  
Lauryn Sperling ◽  
Milagros D. Mulero Alegría ◽  
Volkhard Kaever ◽  
Patrick D. Curtis
Keyword(s):  
Cell Cycle ◽  
Caulobacter Crescentus ◽  
Strain Analysis ◽  
Diguanylate Cyclase ◽  
Critical Function ◽  
Content Type ◽  
Minimal Impact ◽  
Signaling Systems ◽  
Functional Conservation ◽  
Suppressor Mutations

ABSTRACT The DivJ-DivK-PleC signaling system of Caulobacter crescentus is a signaling network that regulates polar development and the cell cycle. This system is conserved in related bacteria, including the sister genus Brevundimonas. Previous studies had shown unexpected phenotypic differences between the C. crescentus divK mutant and the analogous mutant of Brevundimonas subvibrioides, but further characterization was not performed. Here, phenotypic assays analyzing motility, adhesion, and pilus production (the latter characterized by a newly discovered bacteriophage) revealed that divJ and pleC mutants have phenotypes mostly similar to their C. crescentus homologs, but divK mutants maintain largely opposite phenotypes than expected. Suppressor mutations of the B. subvibrioides divK motility defect were involved in cyclic di-GMP (c-di-GMP) signaling, including the diguanylate cyclase dgcB, and cleD which is hypothesized to affect flagellar function in a c-di-GMP dependent fashion. However, the screen did not identify the diguanylate cyclase pleD. Disruption of pleD in B. subvibrioides caused no change in divK or pleC phenotypes, but did reduce adhesion and increase motility of the divJ strain. Analysis of c-di-GMP levels in these strains revealed incongruities between c-di-GMP levels and displayed phenotypes with a notable result that suppressor mutations altered phenotypes but had little impact on c-di-GMP levels in the divK background. Conversely, when c-di-GMP levels were artificially manipulated, alterations of c-di-GMP levels in the divK strain had minimal impact on phenotypes. These results suggest that DivK performs a critical function in the integration of c-di-GMP signaling into the B. subvibrioides cell cycle. IMPORTANCE Cyclic di-GMP and associated signaling proteins are widespread in bacteria, but their role in physiology is often complex and difficult to predict through genomic level analyses. In C. crescentus, c-di-GMP has been integrated into the developmental cell cycle, but there is increasing evidence that environmental factors can impact this system as well. The research presented here suggests that the integration of these signaling networks could be more complex than previously hypothesized, which could have a bearing on the larger field of c-di-GMP signaling. In addition, this work further reveals similarities and differences in a conserved regulatory network between organisms in the same taxonomic family, and the results show that gene conservation does not necessarily imply close functional conservation in genetic pathways.

scholarly journals Spatiotemporal control of PopZ localization through cell cycle–coupled multimerization

2013 ◽  
Vol 201 (6) ◽  
pp. 827-841 ◽  
Author(s):  
Géraldine Laloux ◽  
Christine Jacobs-Wagner
Keyword(s):  
Cell Cycle ◽  
Self Assembly ◽  
Cell Cycle Progression ◽  
Caulobacter Crescentus ◽  
Protein Localization ◽  
Order Structure ◽  
Asymmetric Distribution ◽  
Physiological Processes ◽  
Anchoring Protein ◽  
A Cell

Bacterial cell poles constitute defined subcellular domains where numerous proteins localize, often at specific times, to affect various physiological processes. How pole recognition occurs and what governs the timing of protein localization are often unknown. In this paper, we investigate the mechanisms governing the localization of PopZ, a chromosome-anchoring protein whose unipolar to bipolar localization pattern is critical for cell cycle progression in Caulobacter crescentus. We provide evidence that polar localization of PopZ relied on its self-assembly into a higher-order structure (matrix) and that the unipolar to bipolar transition was coupled to the asymmetric distribution of ParA during the translocation of the origin-proximal ParB–parS partition complex. Collectively, our data suggest a model in which a local increase of ParA concentration promotes the assembly of a PopZ matrix precisely when and where this matrix is needed. Such coupling of protein assembly with a cell cycle–associated molecular asymmetry may represent a principle of cellular organization for controlling protein localization in both time and space.

Research Progress in the Typical Structure of Human Telomeric G-Quadruplex

2014 ◽  
Vol 955-959 ◽  
pp. 419-422
Author(s):  
Gui Lin Liu ◽  
Yan Ping Ding ◽  
Yan Ling Wu ◽  
Wen Zhang
Keyword(s):  
Cell Cycle ◽  
Dna Sequences ◽  
Research Progress ◽  
Human Chromosomes ◽  
Telomeric Dna ◽  
Typical Structure ◽  
Special Sequence ◽  
Physiological Processes ◽  
G Quadruplex ◽  
Small Molecule Ligands

Telomeric DNA of human chromosomes plays a significant role in physiological processes such as cell cycle, aging, cancer and genetic stability due to its special sequence and structure. The research on small molecule ligands targeting G-quadruplex formed by such special sequence has attracted considerable attention, and has achieved great breakthrough. In this paper, we summarize the DNA sequences and structures of three kinds of typical human telomeric G-quadruplex, providing an important reference for further research.

scholarly journals Bacterial cell cycle control by citrate synthase independent of enzymatic activity

2019 ◽  
Author(s):  
Matthieu Bergé ◽  
Julian Pezzatti ◽  
Víctor González-Ruiz ◽  
Laurence Degeorges ◽  
Serge Rudaz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Citrate Synthase ◽  
Caulobacter Crescentus ◽  
Tricarboxylic Acid Cycle ◽  
Cell Cycle Control ◽  
Tca Cycle ◽  
Cell Cycle Regulators ◽  
Central Metabolism ◽  
Cycle Enzyme

ABSTRACTCoordination of cell cycle progression with central metabolism is fundamental to all cell types and likely underlies differentiation into dispersal cells in bacteria. How central metabolism is monitored to regulate cell cycle functions is poorly understood. A forward genetic selection for cell cycle regulators in the polarized alpha-proteobacterium Caulobacter crescentus unearthed the uncharacterized CitA citrate synthase, a TCA (tricarboxylic acid) cycle enzyme, as unprecedented checkpoint regulator of the G1→S transition. We show that loss of the CitA protein provokes a (p)ppGpp alarmone-dependent G1-phase arrest without apparent metabolic or energy insufficiency. While S-phase entry is still conferred when CitA is rendered catalytically inactive, the paralogous CitB citrate synthase has no overt role other than sustaining TCA cycle activity when CitA is absent. With eukaryotic citrate synthase paralogs known to fulfill regulatory functions, our work extends the moonlighting paradigm to citrate synthase coordinating central (TCA) metabolism with development and perhaps antibiotic tolerance in bacteria.

scholarly journals An intracellular compass spatially coordinates cell cycle modules in Caulobacter crescentus

2016 ◽  
Vol 33 ◽  
pp. 131-139 ◽  
Author(s):  
Keren Lasker ◽  
Thomas H Mann ◽  
Lucy Shapiro
Keyword(s):  
Cell Cycle ◽  
Caulobacter Crescentus

scholarly journals Structure of the human TIMP-3 gene and its cell cycle-regulated promoter

1995 ◽  
Vol 311 (2) ◽  
pp. 549-554 ◽  
Author(s):  
M Wick ◽  
R Härönen ◽  
D Mumberg ◽  
C Bürger ◽  
B R Olsen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Alternative Polyadenylation ◽  
Regulatory Elements ◽  
Detailed Knowledge ◽  
Gene Encoding ◽  
Cycle Progression ◽  
Physiological Processes ◽  
Cycle Regulation

The gene encoding tissue inhibitor of metalloproteinases-3 (TIMP-3) is regulated during development, mitogenic stimulation and normal cell cycle progression. The TIMP-3 gene is structurally altered or deregulated in certain diseases of the eye and in tumour cells. A detailed knowledge of the TIMP-3 gene and its regulatory elements is therefore of paramount importance to understand its role in development, cell cycle progression and disease. In this study, we present the complete structure of the human TIMP-3 gene. We show that TIMP-3 is a TATA-less gene, which initiates transcription at one major site, is composed of five exons and four introns spanning a region of approximately 30 kb, and gives rise to three distinct mRNAs, presumably due to the usage of alternative polyadenylation signals. Using somatic cell hybrids the TIMP-3 locus was mapped to chromosomal location 22q13.1 We also show that the TIMP-3 5′ flanking region is sufficient to confer both high basal level expression in growing cells and cell cycle regulation in serum-stimulated cells. While the first 112 bases of the promoter, which harbour multiple Sp1 sites, were found to suffice for high basal level activity, the adjacent region spanning positions -463 and -112 was found to be a major determinant of serum inducibility. These results provide an important basis for further investigations addressing the role of TIMP-3 in physiological processes and pathological conditions.

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