Information processing in the adaptation of Saccharomyces cerevisiae to osmotic stress: an analysis of the phosphorelay system

Uschner, Friedemann; Klipp, Edda

doi:10.1007/s11693-014-9146-6

Cited by 8 publications

(7 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To computationally explore the role of kinetic perturbations in the Sln1-Ypd1 complex on pathway information transmission, we used a modified version of a previously established stochastic model of the Sln1-Ypd1-Ssk1 phosphorelay (Uschner and Klipp, 2014). The model follows a structure as reported by Janiak-Spens et al (2005) and focuses on the stochastic formation of complexes between components of the phosphorelay and on the basal signaling without osmostress ( Figure 1D; Table S1).…”

Section: Predicted Signaling Output Landscape Of Kinetic Perturbationmentioning

confidence: 99%

Interaction Dynamics Determine Signaling and Output Pathway Responses

et al. 2017

Self Cite

View full text Add to dashboard Cite

The understanding of interaction dynamics in signaling pathways can shed light on pathway architecture and provide insights into targets for intervention. Here, we explored the relevance of kinetic rate constants of a key upstream osmosensor in the yeast high-osmolarity glycerol-mitogen-activated protein kinase (HOG-MAPK) pathway to signaling output responses. We created mutant pairs of the Sln1-Ypd1 complex interface that caused major compensating changes in the association (k) and dissociation (k) rate constants (kinetic perturbations) but only moderate changes in the overall complex affinity (K). Yeast cells carrying a Sln1-Ypd1 mutant pair with moderate increases in k and k displayed a lower threshold of HOG pathway activation than wild-type cells. Mutants with higher k and k rates gave rise to higher basal signaling and gene expression but impaired osmoadaptation. Thus, the k and k rates of the components in the Sln1 osmosensor determine proper signaling dynamics and osmoadaptation.

show abstract

Section: Predicted Signaling Output Landscape Of Kinetic Perturbationmentioning

confidence: 99%

Interaction Dynamics Determine Signaling and Output Pathway Responses

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Initially we compiled a list of physiological variables that are important for the function of these signal transduction circuits 9,10,[42][43][44][45][46][47]12,27,[36][37][38][39][40][41] . We compared the alternative architectures to understand how they differed with respect to each of those variables.…”

Section: Discussion Implicationsmentioning

confidence: 99%

What influences selection of native phosphorelay architectures?

Alves

Salvado

Milo³

et al. 2020

Preprint

View full text Add to dashboard Cite

Phosphorelays are signal transduction circuits that combine four different phosphorylatable protein domains for sensing environmental changes and use that information to adjust cellular metabolism to the new conditions in the milieu. Five alternative circuit architectures account for more than 99% of all phosphorelay operons annotated in over 9000 fully sequenced genomes, with one of those architectures accounting for more than 72% of all cases.Here we asked if there are biological design principles that explain the selection of preferred phosphorelay architectures in nature and what might those principles be. We created several types of data-driven mathematical models for the alternative phosphorelay architectures, exploring the dynamic behavior of the circuits in concentration and parameter space, both analytically and through over 10 8 numerical simulations. We compared the behavior of architectures with respect to signal amplification, speed and robustness of the response, noise in the response, and transmission of environmental information to the cell.Clustering analysis of massive Monte Carlo simulations suggests that either information transmission or metabolic cost could be important in selecting the architecture of the phosphorelay. A more detailed study using models of kinetically well characterized phosphorelays (Spo0 of Bacillus subtilis and Sln1-Ypd1-Ssk1-Skn7 of Saccharomyces cerevisiae) shows that information transmission is maximized by the natural architecture of the phosphorelay. In view of this we analyze seventeen additional phosphorelays, for which protein abundance is available but kinetic parameters are not. The architectures of 16 of these are also consistent with maximization of information transmission.Our results highlight the complexity of the genotype (architecture, parameter values, and protein abundance) to phenotype (physiological output of the circuit) mapping in phosphorelays. The results also suggest that maximizing information transmission through the circuit is important in the selection of natural circuit genotypes.3

show abstract

“…This will allow further fine-tuning, e.g. with respect to the role of (anomalous) cytoplasmic diffusion, of systems biology models developed to describe the osmo/stress response in S. cerevisiae (Uschner and Klipp 2014 ; Dexter et al 2015 ). Various super-resolution microscopy techniques are available to facilitate such experiments (e.g.…”

Section: Discussionmentioning

confidence: 99%

Design, characterization and in vivo functioning of a light-dependent histidine protein kinase in the yeast Saccharomyces cerevisiae

Bury

Hellingwerf

2018

AMB Expr

View full text Add to dashboard Cite

Helical alignment of the α-helical linker of the LOV (light-oxygen-voltage) domain of YtvA from Bacillus subtilis with the α-helical linker of the histidine-protein kinase domain of the Sln1 kinase of the phospho-relay system for osmoregulation of Saccharomyces cerevisiae has been used to construct a light-modulatable histidine protein kinase. In vitro, illumination with blue light inhibits both the ATP-dependent phosphorylation of this hybrid kinase, as well as the phosphoryl transfer to Ypd1, the phosphoryl transfer domain of the Sln1 system. The helical alignment was carried out with conservation of the complete Jα helix of YtvA, as well as of the phosphorylatable histidine residue of the Sln1 kinase, with conservation of the hepta-helical motive of coiled-coil structures, recognizable in the helices of the two separate, constituent, proteins. Introduction of the gene encoding this hybrid histidine protein kinase into cells of S. cerevisiae in which the endogenous Sln1 kinase had been deleted, allowed us to modulate gene expression in the yeast cells with (blue) light. This was first demonstrated via the light-induced alteration of the expression level of the mannosyl-transferase OCH1, via a translational-fusion approach. As expected, illumination decreased the expression level of OCH1; the steady state decrease in saturating levels of blue light was about 40%. To visualize the in vivo functionality of this light-dependent regulation system, we fused the green fluorescent protein (GFP) to another regulatory protein, HOG1, which is also responsive to the Sln1 kinase. HOG1 is phosphorylated by the MAP-kinase-kinase Pbs2, which in turn is under control of the Sln1 kinase, via the phosphoryl transfer domain Ypd1. Fluorescence microscopy was used to show that illumination of cells that contained the combination of the hybrid kinase and the HOG1::GFP fusion protein, led to a persistent increase in the level of nuclear accumulation of HOG1, in contrast to salt stress, which—as expected—showed the well-characterized transient response. The system described in this study will be valuable in future studies on the role of cytoplasmic diffusion in signal transduction in eukaryotic cells.Electronic supplementary materialThe online version of this article (10.1186/s13568-018-0582-7) contains supplementary material, which is available to authorized users.

show abstract

Information processing in the adaptation of Saccharomyces cerevisiae to osmotic stress: an analysis of the phosphorelay system

Cited by 8 publications

References 38 publications

Interaction Dynamics Determine Signaling and Output Pathway Responses

Interaction Dynamics Determine Signaling and Output Pathway Responses

What influences selection of native phosphorelay architectures?

Design, characterization and in vivo functioning of a light-dependent histidine protein kinase in the yeast Saccharomyces cerevisiae

Contact Info

Product

Resources

About