Abstract
The yeast Saccharomyces cerevisiae has long been used to produce alcohol from glucose and other sugars. While much is known about glucose metabolism, relatively little is known about the receptors and signaling pathways that indicate glucose availability. Here, we compare the two glucose receptor systems in S. cerevisiae. The first is a heterodimer of transporter-like proteins (transceptors), while the second is a seven-transmembrane receptor coupled to a large G protein (Gpa2) that acts in coordination with two small G proteins (Ras1 and Ras2). Through comprehensive measurements of glucose-dependent transcription and metabolism, we demonstrate that the two receptor systems have distinct roles in glucose signaling: the G-protein-coupled receptor directs carbohydrate and energy metabolism, while the transceptors regulate ancillary processes such as ribosome, amino acids, cofactor and vitamin metabolism. The large G-protein transmits the signal from its cognate receptor, while the small G-protein Ras2 (but not Ras1) integrates responses from both receptor pathways. Collectively, our analysis reveals the molecular basis for glucose detection and the earliest events of glucose-dependent signal transduction in yeast.
Highlights
Most eukaryotic organisms use glucose as the principal source of carbon and energy.Changes in glucose availability result in important metabolic and transcriptional changes that dictate the transition between respiratory and fermentative metabolism [1,2,3,4]
Based on the Venn diagram and over-representation analysis (ORA) analysis, gpa2∆ and ras2∆ had a large number of shared Significantly perturbed metabolites (SPMs) that changed in the same direction, most of which were related to carbohydrate metabolism (Figure 6 and Table S10)
Just as Ras2 acts in synchrony with Gpr1 and Gpa2 to regulate carbohydrate metabolism, we considered if Ras2 works together with Snf3 and Rgt2 to regulate non-carbohydrate species
Summary
Most eukaryotic organisms use glucose as the principal source of carbon and energy. Changes in glucose availability result in important metabolic and transcriptional changes that dictate the transition between respiratory and fermentative metabolism [1,2,3,4]. While the details of glucose metabolism are well understood, we know comparatively little about changes in signal transduction and cellular metabolism in response to glucose availability. These include changes attributed to glucose binding to cell surface receptors and activation of signaling pathways immediately downstream of the receptor but upstream of glycolysis. In this instance, an increase in glucose is transmitted by two distinct processes (Figure 1).
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