Intracellular Maltose Is Sufficient To Induce MAL Gene Expression in Saccharomyces cerevisiae

The presence of maltose induces MAL gene expression in Saccharomyces cells, but little is known about how maltose is sensed. Strains with all maltose permease genes deleted are unable to induce MAL gene expression. In this study, we examined the role of maltose permease in maltose sensing by substituting a heterologous transporter for the native maltose permease. PmSUC2 encodes a sucrose transporter from the dicot plant Plantago major that exhibits no significant sequence homology to maltose permease. When expressed in Saccharomyces cerevisiae, PmSUC2 is capable of transporting maltose, albeit at a reduced rate. We showed that introduction of PmSUC2 restores maltose-inducible MAL gene expression to a maltose permease-null mutant and that this induction requires the MAL activator. These data indicate that intracellular maltose is sufficient to induce MAL gene expression independently of the mechanism of maltose transport. By using strains expressing defective mal61 mutant alleles, we demonstrated a correlation between the rate of maltose transport and the level of the induction, which is particularly evident in medium containing very limiting concentrations of maltose. Moreover, our results indicate that a rather low concentration of intracellular maltose is needed to trigger MAL gene expression. We also showed that constitutive overexpression of either MAL61 maltose permease or PmSUC2 suppresses the noninducible phenotype of a defective mal13 MAL-activator allele, suggesting that this suppression is solely a function of maltose transport activity and is not specific to the sequence of the permease. Our studies indicate that maltose permease does not function as the maltose sensor in S. cerevisiae. Saccharomyces cerevisiae responds to the presence of a wide variety of environmental nutrients via sensing and signaling pathways capable of identifying the nutrients, determining their approximate concentrations, and integrating the informa- tion from these several signals to regulate gene expression and cell growth, proliferation, and morphology. Few nutrient or metabolite sensors have been identified despite extensive ef- forts in a variety of regulated systems. For the most part, those nutrient sensors identified to date fall into two categories: integral membrane receptor-like proteins and cytoplasmic nu- trient/metabolite-binding proteins. Reports suggesting a dual role for certain nutrient transporters as both transporters and sensors have been presented, but conclusive evidence for such, in the form of constitutive alleles of the transporter genes, is lacking (20). We are interested in identifying the Saccharomyces maltose sensor. Previous studies demonstrated that maltose permease plays an essential role in maltose induction of MAL gene ex- pression (5). Moreover, the ability of an -glucoside sugar to serve as an inducer of MAL gene expression appears to be dependent on the substrate specificity of the transporter (15). These results suggested the possibility that the Saccharomyces maltose permease can also play the role of the maltose sensor. Five nearly identical MAL loci have been identified in S. cerevisiae, each located at a telomere-associated site: MAL1 (chromosome VII), MAL2 (chromosome III), MAL3 (chromo-