HOR7, a multicopy suppressor of the Ca2+-induced growth defect in sphingolipid mannosyltransferase-deficient yeast

Yeast mutants defective in sphingolipid mannosylation accumulate inositol phosphorylceramide C (IPC-C), which renders cells Ca2+-sensitive. A screen for loss off function suppressors of the Ca2+-sensitive phenotype previously led to the identification of numerous genes involved in IPC-C synthesis. To better understand the molecular basis of the Ca 2+-induced growth defect in IPC-C-overaccumulating cells, we searched for genes whose overexpression restored Ca2+ tolerance in a mutant lacking the IPC mannosyltransferases Csg1p and Csh1p. Here we report the isolation of HOR7 as a multicopy suppressor of the Ca2+-sensitive phenotype of Δcsg1Δcsh1 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 Ca2+ or Na+ tolerance. Instead, we find that Hor7p-overproducing cells display an increased resistance to high salt, sensitivity to low pH, and a reduced uptake of methyl-ammonium, an indicator of the plasma membrane potential. These phenotypes are induced through a mechanism independent of the plasma membrane H+-ATPase, Pma1p. Our findings suggest that induction of Hor7p causes a depolarization of the plasma membrane that may counteract a Ca2+-induced influx of toxic cations in IPC-C-overaccumuiating cells.