Abstract

PMR1, the Ca 2+/Mn 2+ ATPase of the secretory pathway in Saccharomyces cerevisiae was the first member of the secretory pathway Ca 2+ ATPases (SPCA) to be characterized. In the past few years, pmr1Δ yeast have received more attention due to the recognition that the human homologue of this protein, hSPCA1 is defective in chronic benign pemphigus or Hailey–Hailey disease (HHD). Recent publications have described pmr1Δ S. cerevisiae as a useful model organism for studying the molecular pathology of HHD. Some observations indicated that the high Ca 2+ sensitive phenotype of PMR1 defective yeast strains may be the most relevant in this respect. Here we show that the total cellular calcium response of a pmr1Δ S. cerevisiae upon extracellular Ca 2+ challenge is decreased compared to the wild type strain similarly as observed in keratinocytes. Additionally, the novel magnesium sensitivity of PMR1 defective yeast is revealed, which appears to be a result of competition for uptake between Ca 2+ and Mg 2+ at the plasma membrane level. Our findings indicate that extracellular Ca 2+ and Mg 2+ competitively influence the intracellular Ca 2+ homeostasis of S. cerevisiae. These observations may further our understanding of HHD.

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