Regulatory Network Connecting Two Glucose Signal Transduction Pathways in Saccharomyces cerevisiae

Abstract

The yeast Saccharomyces cerevisiae senses glucose, its preferred carbon source, through multiple signal transduction pathways. In one pathway, glucose represses the expression of many genes through the Mig1 transcriptional repressor, which is regulated by the Snf1 protein kinase. In another pathway, glucose induces the expression of HXT genes encoding glucose transporters through two glucose sensors on the cell surface that generate an intracellular signal that affects function of the Rgt1 transcription factor. We profiled the yeast transcriptome to determine the range of genes targeted by this second pathway. Candidate target genes were verified by testing for Rgt1 binding to their promoters by chromatin immunoprecipitation and by measuring the regulation of the expression of promoter lacZ fusions. Relatively few genes could be validated as targets of this pathway, suggesting that this pathway is primarily dedicated to regulating the expression of HXT genes. Among the genes regulated by this glucose signaling pathway are several genes involved in the glucose induction and glucose repression pathways. The Snf3/Rgt2-Rgt1 glucose induction pathway contributes to glucose repression by inducing the transcription of MIG2, which encodes a repressor of glucose-repressed genes, and regulates itself by inducing the expression of STD1, which encodes a regulator of the Rgt1 transcription factor. The Snf1-Mig1 glucose repression pathway contributes to glucose induction by repressing the expression of SNF3 and MTH1, which encodes another regulator of Rgt1, and also regulates itself by repressing the transcription of MIG1. Thus, these two glucose signaling pathways are intertwined in a regulatory network that serves to integrate the different glucose signals operating in these two pathways.

Endocytosis and Vacuolar Degradation of the Yeast Cell Surface Glucose Sensors Rgt2 and Snf3

“…2). We have previously shown that that Mig1 and Mig2 repressors mediate glucose repression of SNF3 gene expression (17,28). Therefore, glucose-induced Snf3 degradation is reinforced by glucose repression of SNF3 gene expression, but glucose depletion-induced Snf3 degradation is dampened by derepression of SNF3 gene expression.…”

“…2B and Ref. 28), we further examined whether Snf3 abundance is regulated at both the transcriptional and post-translational levels. To this end, we expressed GFP-Snf3 under the control of the MET25 promoter, which is not regulated by glucose (17,22).…”

Two Glucose-sensing Pathways Converge on Rgt1 to Regulate Expression of Glucose Transporter Genes in Saccharomyces cerevisiae

“…Std1 does not completely disappear when glucose is added to cells because glucose induces expression of STD1 (via the Snf3/ Rgt2-Rgt1 glucose signaling pathway (12,33)). Enough Std1 could remain in glucose-grown cells to attenuate the intramolecular interaction of Rgt1, and this would dampen induction of HXT expression.…”

Glucose sensing and signaling in Saccharomyces cerevisiae through the Rgt2 glucose sensor and casein kinase I

“…We believe this difference is due to the different regulation of MTH1 and STD1 expression. STD1 expression is induced by glucose [via the Rgt2͞Snf3-Rgt1 pathway (33)], which would be expected to counteract Std1 degradation. However, glucose increases STD1 expression at the same time that it induces its degradation.…”

“…However, glucose increases STD1 expression at the same time that it induces its degradation. MTH1 expression, on the other hand, is repressed by glucose [via the Snf1-Mig1 pathway, (33)], which would be expected to reinforce Mth1 degradation, but glucose reduces MTH1 expression at the same time that it stimulates its degradation. The relative resistance of Std1 to degradation may account for the different roles in regulation of HXT expression that are apparent for Mth1 and Std1 (8).…”