Cytosolic free Ca2+ is maintained at submicromolar levels in budding y
east by the activity of Ca2+ pumps and antiporters. We have recently i
dentified the structural genes for two Ca2+ pumps, PCM1 and PMR1, whic
h are required for Ca2+ sequestration into the vacuole and secretory o
rganelles, respectively. The function of either Ca2+ pump is sufficien
t for yeast viability, but deletion of both genes is lethal because of
elevation of cytosolic [Ca2+] and activation of calcineurin, a Ca2+-
and calmodulin-dependent protein phosphatase. Calcineurin activation d
ecreases Ca2+ sequestration in the vacuole by a putative Ca2+ antiport
er and may also increase Ca2+ pump activity. These regulatory processe
s can affect the ability of yeast strains to tolerate high extracellul
ar [Ca2+]. We propose a model in which the cellular response to change
s in the environmental levels of Ca2+ is mediated by calmodulin and ca
lcineurin which, in turn, modulate the various types of Ca2+ transport
ers.