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Yeast glucose pathways converge on the transcriptional regulation of trehalose biosynthesis.

Apweiler E, Sameith K, Margaritis T, Brabers N, van de Pasch L, Bakker LV, van Leenen D, Holstege FC, Kemmeren P - BMC Genomics (2012)

Bottom Line: In general, the mutations do not induce pathway-specific transcriptional responses.Epistasis analysis of tps2Δ double mutants supports this prediction.Although based on transcriptional changes only, these results suggest that all changes in perceived glucose levels ultimately lead to a shift in trehalose biosynthesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Molecular Cancer Research, University Medical Centre Utrecht, Utrecht, the Netherlands.

ABSTRACT

Background: Cellular glucose availability is crucial for the functioning of most biological processes. Our understanding of the glucose regulatory system has been greatly advanced by studying the model organism Saccharomyces cerevisiae, but many aspects of this system remain elusive. To understand the organisation of the glucose regulatory system, we analysed 91 deletion mutants of the different glucose signalling and metabolic pathways in Saccharomyces cerevisiae using DNA microarrays.

Results: In general, the mutations do not induce pathway-specific transcriptional responses. Instead, one main transcriptional response is discerned, which varies in direction to mimic either a high or a low glucose response. Detailed analysis uncovers established and new relationships within and between individual pathways and their members. In contrast to signalling components, metabolic components of the glucose regulatory system are transcriptionally more frequently affected. A new network approach is applied that exposes the hierarchical organisation of the glucose regulatory system.

Conclusions: The tight interconnection between the different pathways of the glucose regulatory system is reflected by the main transcriptional response observed. Tps2 and Tsl1, two enzymes involved in the biosynthesis of the storage carbohydrate trehalose, are predicted to be the most downstream transcriptional components. Epistasis analysis of tps2Δ double mutants supports this prediction. Although based on transcriptional changes only, these results suggest that all changes in perceived glucose levels ultimately lead to a shift in trehalose biosynthesis.

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An overview of the yeast glucose signalling and metabolic pathways. Signalling events are indicated in solid black, metabolic reactions in solid grey lines. Dashed black lines imply glucose signals activating the signalling components, dashed grey lines summarise metabolic reactions, e.g. glycolysis and gluconeogenesis. The metabolic pathways synthesising the storage carbohydrates glycogen and trehalose are depicted in detail. † indicates that the deletion mutant is lethal.
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Figure 1: An overview of the yeast glucose signalling and metabolic pathways. Signalling events are indicated in solid black, metabolic reactions in solid grey lines. Dashed black lines imply glucose signals activating the signalling components, dashed grey lines summarise metabolic reactions, e.g. glycolysis and gluconeogenesis. The metabolic pathways synthesising the storage carbohydrates glycogen and trehalose are depicted in detail. † indicates that the deletion mutant is lethal.

Mentions: Many organisms have evolved survival strategies centred on glucose as their chief cellular carbon and energy source. Cellular glucose availability governs most biological processes such as growth, division, metabolism and the ability to deal with environmental stresses. Our understanding of glucose signalling in eukaryotes has been greatly advanced by studying the model organism Saccharomyces cerevisiae. Despite its relative simplicity, yeast has developed a complex system to monitor external glucose levels and faithfully relay this information to adjust metabolic and gene expression programmes accordingly. There are in fact several distinct upstream regulatory pathways for glucose regulation, including the Ras/PKA, Gpr1/PKA, Sch9, Yak1, Snf1 and Snf3/Rgt2 signalling pathways, as well as the metabolic pathways (Figure 1; for comprehensive reviews, see [1,2]). Although transmission of the glucose signal is thought to be redundant [1,3], each pathway possesses distinct glucose detection and signal transmission methods.


Yeast glucose pathways converge on the transcriptional regulation of trehalose biosynthesis.

Apweiler E, Sameith K, Margaritis T, Brabers N, van de Pasch L, Bakker LV, van Leenen D, Holstege FC, Kemmeren P - BMC Genomics (2012)

An overview of the yeast glucose signalling and metabolic pathways. Signalling events are indicated in solid black, metabolic reactions in solid grey lines. Dashed black lines imply glucose signals activating the signalling components, dashed grey lines summarise metabolic reactions, e.g. glycolysis and gluconeogenesis. The metabolic pathways synthesising the storage carbohydrates glycogen and trehalose are depicted in detail. † indicates that the deletion mutant is lethal.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472246&req=5

Figure 1: An overview of the yeast glucose signalling and metabolic pathways. Signalling events are indicated in solid black, metabolic reactions in solid grey lines. Dashed black lines imply glucose signals activating the signalling components, dashed grey lines summarise metabolic reactions, e.g. glycolysis and gluconeogenesis. The metabolic pathways synthesising the storage carbohydrates glycogen and trehalose are depicted in detail. † indicates that the deletion mutant is lethal.
Mentions: Many organisms have evolved survival strategies centred on glucose as their chief cellular carbon and energy source. Cellular glucose availability governs most biological processes such as growth, division, metabolism and the ability to deal with environmental stresses. Our understanding of glucose signalling in eukaryotes has been greatly advanced by studying the model organism Saccharomyces cerevisiae. Despite its relative simplicity, yeast has developed a complex system to monitor external glucose levels and faithfully relay this information to adjust metabolic and gene expression programmes accordingly. There are in fact several distinct upstream regulatory pathways for glucose regulation, including the Ras/PKA, Gpr1/PKA, Sch9, Yak1, Snf1 and Snf3/Rgt2 signalling pathways, as well as the metabolic pathways (Figure 1; for comprehensive reviews, see [1,2]). Although transmission of the glucose signal is thought to be redundant [1,3], each pathway possesses distinct glucose detection and signal transmission methods.

Bottom Line: In general, the mutations do not induce pathway-specific transcriptional responses.Epistasis analysis of tps2Δ double mutants supports this prediction.Although based on transcriptional changes only, these results suggest that all changes in perceived glucose levels ultimately lead to a shift in trehalose biosynthesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Molecular Cancer Research, University Medical Centre Utrecht, Utrecht, the Netherlands.

ABSTRACT

Background: Cellular glucose availability is crucial for the functioning of most biological processes. Our understanding of the glucose regulatory system has been greatly advanced by studying the model organism Saccharomyces cerevisiae, but many aspects of this system remain elusive. To understand the organisation of the glucose regulatory system, we analysed 91 deletion mutants of the different glucose signalling and metabolic pathways in Saccharomyces cerevisiae using DNA microarrays.

Results: In general, the mutations do not induce pathway-specific transcriptional responses. Instead, one main transcriptional response is discerned, which varies in direction to mimic either a high or a low glucose response. Detailed analysis uncovers established and new relationships within and between individual pathways and their members. In contrast to signalling components, metabolic components of the glucose regulatory system are transcriptionally more frequently affected. A new network approach is applied that exposes the hierarchical organisation of the glucose regulatory system.

Conclusions: The tight interconnection between the different pathways of the glucose regulatory system is reflected by the main transcriptional response observed. Tps2 and Tsl1, two enzymes involved in the biosynthesis of the storage carbohydrate trehalose, are predicted to be the most downstream transcriptional components. Epistasis analysis of tps2Δ double mutants supports this prediction. Although based on transcriptional changes only, these results suggest that all changes in perceived glucose levels ultimately lead to a shift in trehalose biosynthesis.

Show MeSH