Role of signal transduction pathways in the regulation of lipid metabolism in S. cerevisiae

Abstract

The INO1 gene is the most highly regulated of a group of co-regulated genes involved in phospholipid biosynthesis in yeast that contain the repeated element UASINO in their promoter. Our observations suggest that the complex regulation of INO1 and other UASINO-containing genes is due to the combinatorial inputs of several signal transduction pathways. We report here that mutants defective in the PKC-mediated cell integrity pathway, including pkc1Δ, bck1Δ and mpk1Δ, exhibit inositol auxotrophy (Ino−phenotype), indicative of defects in INO1 expression. The opi1 mutation confers high-level constitutive INO1 expression, indicated by the Opi− phenotype (for overproduction of inositol). Deletion of the OPI1 gene in the pck1, bck1, and mpk1 mutants suppresses their Ino− phenotype, and confers an Opi−phenotype. Our preliminary results indicate that the mpk1 mutation results in abnormal INO1 expression. Deleting MPK1 also results in an abnormal accumulation of certain lipid species. A screen for high copy suppressors of the mpk1Δ Ino− phenotype identified NTE1. The NTE1 gene encodes a phospholipase type B that deacylates phosphatidylcholine (PC) to glycerophosphocholine. The potential PKC pathway-mediated regulation of lipid turnover, specifically deacylation of PC, is currently under investigation. Supported by a grant of the National Institutes of Health to S.A.H. (GM019629-31).