The role and regulation of glycogen synthesis in Saccharomyces cerevisiae

Glycogen synthesis is a complex process under both transcriptional and post-translational control. One major regulatory mechanism is phosphorylation. Dephosphorylation of glycogen synthase and glycogen phophorylase, performed by PP1, stimulates glycogen synthesis. PP1 is encoded in yeast by GLC7. glc7-1, a PP1 mutant which cannot stimulate glycogen synthesis but performs all essential functions of PP1 was used to identify mutations in control points of glycogen synthesis. All the mutations recovered occurred in GSY2, the gene for the major glycogen synthase in S. cerevisiae. Twelve unique mutations were identified, which fall into three groups. One of these groups occurs in a phosphoregulatory region and the other two occur in novel regions.; The increased glycogen observed in these mutants is not specific to glc7-1. Increased glycogen was also observed in a GLC7 background and in conjunction with several mutations which reduce glycogen accumulation, including gac1, snf1 and rho-, but not bcy1. The mutants are not completely deregulated, since the overall pattern of glycogen accumulation is similar to wild type. Overaccumulation is not due to increased expression, as these mutants are expressed at lower levels than the wild type. Mutants in the phosphoregulatory domain exhibit decreased phosphorylation, and are likely to function by preventing inactivation. The remaining groups are as or more phosphorylated than the wild type, and must function in some other manner.; Glycogen accumulates in response to decreases in extracellular nutrients such as glucose, phosphate, or nitrogen, suggesting that it may be important under nutrient limiting conditions. However, disruption of both isoforms of glycogen synthase completely prevents glycogen accumulation but causes no apparent growth defect. Co-cultivation experiments show that glycogen accumulation is important to the relative fitness of S. cerevisiae. Defects in glycogen accumulation do not alter accumulation of trehalose, the other major storage carbohydrate in yeast. However, as shown here, alterations in glycogen result in decreased viability in stationary phase and changes in management of lipid stores.