Rabbit sarcoplasmic reticulum Ca(2+)-ATPase replaces yeast PMC1 and PMR1 Ca(2+)-ATPases for cell viability and calcineurin-dependent regulation of calcium tolerance

Mol Microbiol. 1999 Jan;31(2):545-56. doi: 10.1046/j.1365-2958.1999.01195.x.


SERCA1a, the fast-twitch skeletal muscle isoform of sarco(endo)plasmic reticulum Ca(2+)-ATPase, was expressed in yeast using the promoter of the plasma membrane H(+)-ATPase. In the yeast Saccharomyces cerevisiae, the Golgi PMR1 Ca(2+)-ATPase and the vacuole PMC1 Ca(2+)-ATPase function together in Ca2+ sequestration and Ca2+ tolerance. SERCA1a expression restored growth of pmc1 mutants in media containing high Ca2+ concentrations, consistent with increased Ca2+ uptake in an internal compartment. SERCA1a expression also prevented synthetic lethality of pmr1 pmc1 double mutants on standard media. Electron microscopy and subcellular fractionation analysis showed that SERCA1a was localized in intracellular membranes derived from the endoplasmic reticulum. Finally, we found that SERCA1a ATPase activity expressed in yeast was regulated by calcineurin, a Ca2+/calmodulin-dependent phosphoprotein phosphatase. This result indicates that calcineurin contributes to calcium homeostasis by modulating the ATPase activity of Ca2+ pumps localized in intra-cellular compartments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Calcineurin / metabolism*
  • Calcium / metabolism
  • Calcium-Transporting ATPases / genetics
  • Calcium-Transporting ATPases / metabolism*
  • Fungal Proteins / metabolism*
  • Gene Expression
  • Intracellular Membranes / metabolism
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Molecular Chaperones
  • Phosphoproteins / metabolism
  • Plasma Membrane Calcium-Transporting ATPases
  • Rabbits
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins*
  • Sarcoplasmic Reticulum / enzymology*


  • ATP-Binding Cassette Transporters
  • Fungal Proteins
  • Isoenzymes
  • Molecular Chaperones
  • PMC1 protein, S cerevisiae
  • Phosphoproteins
  • SSC1 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Calcineurin
  • Plasma Membrane Calcium-Transporting ATPases
  • Calcium-Transporting ATPases
  • Calcium