Std1 and Mth1 Proteins Interact with the Glucose Sensors To Control Glucose-Regulated Gene Expression in Saccharomyces cerevisiae

Abstract

The Std1 protein modulates the expression of glucose-regulated genes, but its exact molecular role in this process is unclear. A two-hybrid screen for Std1-interacting proteins identified the hydrophilic C-terminal domains of the glucose sensors, Snf3 and Rgt2. The homologue of Std1, Mth1, behaves differently from Std1 in this assay by interacting with Snf3 but not Rgt2. Genetic interactions between STD1, MTH1, SNF3, and RGT2 suggest that the glucose signaling is mediated, at least in part, through interactions of the products of these four genes. Mutations in MTH1 can suppress the raffinose growth defect of a snf3 mutant as well as the glucose fermentation defect present in cells lacking both glucose sensors (snf3 rgt2). Genetic suppression by mutations in MTH1 is likely to be due to the increased and unregulated expression of hexose transporter genes. In media lacking glucose or with low levels of glucose, the hexose transporter genes are subject to repression by a mechanism that requires the Std1 and Mth1 proteins. An additional mechanism for glucose sensing must exist since a strain lacking all four genes (snf3 rgt2 std1 mth1) is still able to regulate SUC2 gene expression in response to changes in glucose concentration. Finally, studies with green fluorescent protein fusions indicate that Std1 is localized to the cell periphery and the cell nucleus, supporting the idea that it may transduce signals from the plasma membrane to the nucleus.

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

“…3). These results, together with the knowledge that Mth1 and Std1 bind to the C-terminal cytoplasmic tails of the glucose sensors (7,8), lead us to propose that glucose binding to Rgt2 (and Snf3) activates Yck1 (and Yck2), which then catalyzes phosphorylation of Mth1 and Std1 bound to the tails of the glucose sensors (Fig. 4).…”

“…These results lead us to conclude that the sensor tails are not required for its ability to signal. We imagine that the role of the sensor tails is to recruit Mth1 and Std1 (7,8) to the vicinity of a protein that modulates their activity and that is activated by the transmembrane domain of the glucose-bound sensors. We suggest that enough Mth1 and Std1 happen to reside near the (overexpressed) tailless sensor for them to be inhibited by the unknown protein that is coupled to the sensors.…”

“…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).…”

“…Repression of transcription by Rgt1 also requires the paralogous proteins Mth1 and Std1 (3,5). Because Mth1 and Std1 interact with both the Rgt1 repressor (5,6) and the Snf3 and Rgt2 glucose sensors (7,8), they are good candidates for the components of the signal transduction pathway that are inhibited by the glucose signal. Indeed, it was recently reported that Mth1 is degraded when glucose is added to cells by SCF Grr1 (3).…”

Glucose-mediated Phosphorylation Converts the Transcription Factor Rgt1 from a Repressor to an Activator

“…Two homologous proteins, Std1 and Mth1, have been shown to negatively regulate HXT gene expression and to interact with the carboxyl-terminal tails of the Snf3 and Rgt2 sensors (9 -11). Repression of HXT gene expression in the absence of glucose is abolished in a std1 mth1 double mutant (9,11).…”