Abstract
The yeast Saccharomyces cerevisiae employs multiple pathways to coordinate sugar availability and metabolism. Glucose and other sugars are detected by a G protein-coupled receptor, Gpr1, as well as a pair of transporter-like proteins, Rgt2 and Snf3. When glucose is limiting, however, an ATP-driven proton pump (Pma1) is inactivated, leading to a marked decrease in cytoplasmic pH. Here we determine the relative contribution of the two sugar-sensing pathways to pH regulation. Whereas cytoplasmic pH is strongly dependent on glucose abundance and is regulated by both glucose-sensing pathways, ATP is largely unaffected and therefore cannot account for the changes in Pma1 activity. These data suggest that the pH is a second messenger of the glucose-sensing pathways. We show further that different sugars differ in their ability to control cellular acidification, in the manner of inverse agonists. We conclude that the sugar-sensing pathways act via Pma1 to invoke coordinated changes in cellular pH and metabolism. More broadly, our findings support the emerging view that cellular systems have evolved the use of pH signals as a means of adapting to environmental stresses such as those caused by hypoxia, ischemia, and diabetes.
Highlights
The yeast Saccharomyces cerevisiae employs multiple pathways to coordinate sugar availability and metabolism
When preferred sugars are in short supply, the resulting changes in metabolism are mediated by the protein kinase Snf1, the founding member of the AMP-activated protein kinase (AMPK)3 family [1, 2]
protein kinase (PKA) is activated by cAMP, a second messenger generated from ATP by the adenylyl cyclase enzyme Cyr1 [3,4,5,6]
Summary
The yeast Saccharomyces cerevisiae employs multiple pathways to coordinate sugar availability and metabolism. Whereas cytoplasmic pH is strongly dependent on glucose abundance and is regulated by both glucose-sensing pathways, ATP is largely unaffected and cannot account for the changes in Pma activity. These data suggest that the pH is a second messenger of the glucose-sensing pathways. We conclude that the sugar-sensing pathways act via Pma to invoke coordinated changes in cellular pH and metabolism. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Two other protein kinase systems, considered here, coordinate the response to glucose availability and thereby act in opposition to Snf. It is not known how Cdc and Sdc are themselves activated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
