Calcium and magnesium competitively influence the growth of a PMR1 deficient Saccharomyces cerevisiae strain

PMR1, the Ca²⁺/Mn²⁺ ATPase of the secretory pathway in Saccharomyces cerevisiae was the first member of the secretory pathway Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ and Mg²⁺ at the plasma membrane level. Our findings indicate that extracellular Ca²⁺ and Mg²⁺ competitively influence the intracellular Ca²⁺ homeostasis of S. cerevisiae. These observations may further our understanding of HHD.