HOR7, a Multicopy Suppressor of the Ca super(2+)-induced Growth Defect in Sphingolipid Mannosyltransferase-deficient Yeast

• Published in: The Journal of biological chemistry Vol. 279; no. 35; pp. 36390 - 36396
• Main Authors: Lisman, Quirine, Urli-Stam, Dorothy, Holthuis, Joost CM
• Format: Journal Article
• Language: English
• Published: 27.08.2004
• Subjects: Saccharomyces cerevisiae
• ISSN: 0021-9258; 1083-351X

Yeast mutants defective in sphingolipid mannosylation accumulate inositol phosphorylceramide C (IPC-C), which renders cells Ca super(2+)-sensitive. A screen for loss of function suppressors of the Ca super(2+)-sensitive phenotype previously led to the identification of numerous genes involved in IPC-C synthesis. To better understand the molecular basis of the Ca super(2+)-induced growth defect in IPC-C-overaccumulating cells, we searched for genes whose overexpression restored Ca super(2+) tolerance in a mutant lacking the IPC mannosyltransferases Csg1p and Csh1p. Here we report the isolation of HOR7 as a multicopy suppressor of the Ca super(2+)-sensitive phenotype of deltacsg1deltacsh1 cells. HOR7 belongs to a group of hyperosmolarity-responsive genes and encodes a small (59-residue) type I membrane protein that localizes at the plasma membrane. Hor7p is not required for high Ca super(2+) or Na super(+) tolerance. Instead, we find that Hor7p- overproducing cells display an increased resistance to high salt, sensitivity to low pH, and a reduced uptake of methylammonium, an indicator of the plasma membrane potential. These phenotypes are induced through a mechanism independent of the plasma membrane H super(+)-ATPase, Pma1p. Our findings suggest that induction of Hor7p causes a depolarization of the plasma membrane that may counteract a Ca super(2+)-induced influx of toxic cations in IPC-C-overaccumulating cells.