PMC1 encodes a Ca2+ ATPase that transports calcium from the cytoplasm into the vacuole and participates in calcium homeostasis. S. cerevisiae contains two Ca2+ ATPases: Pmc1p and Pmr1p(1). Pmr1p is the principal Ca2+ ATPase that is expressed under normal growth conditions and Pmc1p is induced in the absence of PMR1 or with calcium overload (2).

PMC1 gene is not essential for viability under normal growth conditions and disruption of PMC1 does not affect mating, sporulation or starvation. Deleting PMC1 results in a large reduction of nonexchangeable Ca2+ pool in the vacuole and in high cellular Ca2+ concentrations pmc1 mutants exhibits growth inhibition. Ca2+ sequestration in the vacuole can be restored by the inactivation of calcineurin complex, a Ca2+/calmodulin-dependent protein phosphatase sensitive to the immunosuppressive drug FK506. Simultaneous deletion of CNA1 and CMP2 encoding the catalytic subunits of calcineurin restores the growth of the pmc1 mutants. Disruption of CNB1, the regulatory subunit of calcineurin, also restores the growth of pmc1 mutants (1, 2). Calcineurin decreases Ca2+ tolerance of pmc1 mutants by inhibiting the function of VCX1, which encodes a vacuolar H+/Ca2+ exchanger, possibly at a post-translational level (4).

Transcription of PMC1 and PMR1 is increased upon calcineurin-dependent activation of the transcription factor Crz1p (5, 6). In high Ca2+ environments, the strong up-regulation of PMC1 is necessary for growth, however, when the Ca2+ concentrations subside, the excess Pmc1p activity is negatively regulated by Nyv1p, a vacuolar v-SNARE protein. Overexpression of Nyv1p does not decrease Pmc1p levels but decreases the specific ATP-dependent Ca2+ transport activity of Pmc1p in purified vacuoles by at least 2-fold. Nyv1p binds to Pmc1p and inhibits its Ca2+ transport activity in vivo and in vitro (7).

Pmc1p shares sequence similarity with mammalian PMCA1a, PMC1 in S. pombe and the Ca2+ ATPases of T. brucei and A. thaliana(1, 8, 9).

Last updated: 2006-11-03