Cell Wall Integrity MAPK Pathway Is Essential for Lipid Homeostasis

• Published in: The Journal of biological chemistry Vol. 283; no. 49; pp. 34204 - 34217
• Main Authors: Nunez, Lilia R., Jesch, Stephen A., Gaspar, Maria L., Almaguer, Claudia, Villa-Garcia, Manuel, Ruiz-Noriega, Monica, Patton-Vogt, Jana, Henry, Susan A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.12.2008; American Society for Biochemistry and Molecular Biology
• Subjects: Cell Membrane - enzymology; Cell Wall - enzymology; Genotype; Lipids - chemistry; MAP Kinase Signaling System; Mutation; Oligonucleotide Array Sequence Analysis; Phenotype; Phosphatidylcholines - chemistry; Phosphatidylinositols - chemistry; Phospholipids - chemistry; Plasmids - metabolism; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - metabolism; Signal Transduction; Temperature
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M806391200

The highly conserved yeast cell wall integrity mitogen-activated protein kinase pathway regulates cellular responses to cell wall and membrane stress. We report that this pathway is activated and essential for viability under growth conditions that alter both the abundance and pattern of synthesis and turnover of membrane phospholipids, particularly phosphatidylinositol and phosphatidylcholine. Mutants defective in this pathway exhibit a choline-sensitive inositol auxotrophy, yet fully derepress INO1 and other Opi1p-regulated genes when grown in the absence of inositol. Under these growth conditions, Mpk1p is transiently activated by phosphorylation and stimulates the transcription of known targets of Mpk1p signaling, including genes regulated by the Rlm1p transcription factor. mpk1Δ cells also exhibit severe defects in lipid metabolism, including an abnormal accumulation of phosphatidylcholine, diacylglycerol, triacylglycerol, and free sterols, as well as aberrant turnover of phosphatidylcholine. Overexpression of the NTE1 phospholipase B gene suppresses the choline-sensitive inositol auxotrophy of mpk1Δ cells, whereas overexpression of other phospholipase genes has no effect on this phenotype. These results indicate that an intact cell wall integrity pathway is required for maintaining proper lipid homeostasis in yeast, especially when cells are grown in the absence of inositol.