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 Ca(2+)-sensitive. A screen for loss of function suppressors of the Ca(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(2+)-induced growth defect in ... IPC-C-overaccumulating cells, we searched for genes whose overexpression restored Ca(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(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(2+) 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 methylammonium, 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 Ca(2+)-induced influx of toxic cations in IPC-C-overaccumulating cells.
Mesh Terms:
Adenosine Triphosphatases, Amino Acid Sequence, Blotting, Western, Calcium, Cell Division, Cell Membrane, Fungal Proteins, Glycosyltransferases, Hydrogen-Ion Concentration, Mannosyltransferases, Membrane Proteins, Methylamines, Microscopy, Fluorescence, Models, Biological, Models, Genetic, Molecular Sequence Data, Phenotype, Plasmids, Protein Structure, Tertiary, Proton-Translocating ATPases, Repressor Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Sodium, Sphingolipids, Subcellular Fractions, Time Factors
Adenosine Triphosphatases, Amino Acid Sequence, Blotting, Western, Calcium, Cell Division, Cell Membrane, Fungal Proteins, Glycosyltransferases, Hydrogen-Ion Concentration, Mannosyltransferases, Membrane Proteins, Methylamines, Microscopy, Fluorescence, Models, Biological, Models, Genetic, Molecular Sequence Data, Phenotype, Plasmids, Protein Structure, Tertiary, Proton-Translocating ATPases, Repressor Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Sodium, Sphingolipids, Subcellular Fractions, Time Factors
J. Biol. Chem.
Date: Aug. 27, 2004
PubMed ID: 15208314
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