# Receptor-mediated glucose sensing in yeast

> **NIH NIH R15** · COLUMBIA INTERNATIONAL UNIVERSITY · 2024 · $327,263

## Abstract

SUMMARY
Because glucose is the principal carbon and energy source for most cells, organisms have evolved numerous
and sophisticated mechanisms for sensing glucose and responding to it appropriately. Impaired regulation of
blood glucose levels, due to defects in glucose sensing, may cause severe metabolic disorders, such as
diabetes, and many types of cancer cells depend on a high rate of glucose consumption to maintain their
viability. Glucose sensing and signaling is of great significance to yeast, because it contributes to distinctive
fermentative metabolism of yeast, a lifestyle it shares with many kinds of tumor cells. Our long-term goal is to
understand how eukaryotic cells sense extracellular glucose and adapt their central metabolic pathways to
better suit the availability of this crucial fuel using the yeast S. cerevisiae as a model system. Energy
generation by fermentation of glucose is inefficient, requiring yeast cells to pump large amounts of glucose
through glycolysis. They do this by enhancing the rate-limiting step of glucose metabolism, its transport. Yeast
cells have learned how to sense the amount of extracellular glucose available and respond by expressing the
most appropriate of its 17 glucose transporters. Expression of the glucose transporter genes (HXTs) is
repressed by the Rgt1 transcription factor, which forms a repressor complex with its corepressors Mth1 and
Std1 and the general corepressors Ssn6/Tup1 on the HXT promoters in the absence of glucose. Glucose
induction of HXT expression is achieved through a signal transduction pathway that begins at the cell surface
with the Rgt2 and Snf3 glucose sensing receptors (GSRs) and ends in the nucleus with Rgt1.The general
outline of this pathway was in place at the beginning of the last funding period. It was clear that the GSRs
generate an intracellular signal in response to glucose that alters the function of the Rgt1 repressor by causing
proteasomal degradation of Mh1 and Std1, and that signal generation is receptor-mediated, because glucose
metabolism is not necessary for its generation. What was less clearly understood was how the glucose signal
is transduced from the GSRs to Mth1 and Std1. The Ycks (the yeast orthologs of mammalian CK1) were
suggested to be coupled to the GSRs and act as downstream effectors of the GSRs, but genetic epistasis and
biochemical analyses place the Ycks upstream of the GSRs. There are crucial gaps in our understanding of
how the signal is generated and transduced from the cell surface to the cytosol. Over the next three years, our
efforts will be devoted to filling the gaps and developing a new model for this glucose signal transduction
pathway.

## Key facts

- **NIH application ID:** 10974735
- **Project number:** 2R15GM134447-02
- **Recipient organization:** COLUMBIA INTERNATIONAL UNIVERSITY
- **Principal Investigator:** Jeong-Ho Kim
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $327,263
- **Award type:** 2
- **Project period:** 2019-07-02 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10974735

## Citation

> US National Institutes of Health, RePORTER application 10974735, Receptor-mediated glucose sensing in yeast (2R15GM134447-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10974735. Licensed CC0.

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