Cytosolic free Ca2+ is maintained at submicromolar levels in budding yeast by the activity of Ca2+ pumps and antiporters. We have recently identified the structural genes for two Ca2+ pumps, PMC1 [correction of PCM1] and PMR1, which are required for Ca2+ sequestration into the vacuole and secretory organelles, respectively. The function of either Ca2+ pump is sufficient for yeast viability, but deletion of both genes is lethal because of elevation of cytosolic [Ca2+] and activation of calcineurin, a Ca(2+)- and calmodulin-dependent protein phosphatase. Calcineurin activation decreases Ca2+ sequestration in the vacuole by a putative Ca2+ antiporter and may also increase Ca2+ pump activity. These regulatory processes can affect the ability of yeast strains to tolerate high extracellular [Ca2+]. We propose a model in which the cellular response to changes in the environmental levels of Ca2+ is mediated by calmodulin and calcineurin which, in turn, modulate the various types of Ca2+ transporters.

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