Glucose Sensing and Signal Transduction in Saccharomyces cerevisiae

Cells of the yeast Saccharomyces cerevisiae have an exquisite preference for high concentrations of glucose compared to other sugars or carbon sources. The likely explanation is that glucose is the best fermentable sugar, i.e., the sugar that allows the yeast to accumulate most rapidly high levels of ethanol, which are strongly inhibitory to competing microorganisms. To accomplish rapid fermentation of glucose, S. cerevisiae has evolved multiple glucose sensing and signaling pathways, which stimulate both fermentation and rapid cell proliferation. The latter is important for rapid fermentation in order to recycle the ATP generated in glycolysis to ADP. Downregulation of respiration to maximize ethanol production is accomplished by the main glucose repression pathway, in which the Snf1 protein kinase is a central regulator. It is inactivated by dephosphorylation upon glucose addition, and its reactivation upon glucose exhaustion is essential for induction of genes sustaining respiration, gluconeogenesis, and the catabolism of alternative carbon sources. Stimulation of fermentation and growth is mainly exerted by the protein kinase A pathway, which senses glucose with an extracellular and intracellular sensing mechanism that activates protein kinase A in a concerted manner through stimulation of cAMP synthesis. Sensing of other nutrients by plasma membrane transceptors integrates with this glucose-sensing mechanism to maintain high protein kinase A activity throughout fermentative growth. Induction of appropriate glucose transporters during fermentative growth is controlled by plasma membrane transporter-like proteins, which function as glucose sensors. Although detailed knowledge has been gained on the molecular mechanisms involved in glucose signaling, multiple important questions still remain.status: publishe