Extracellular Ca(2+) sensing contributes to excess Ca(2+) accumulation and vacuolar fragmentation in a pmr1Delta mutant of S. cerevisiae.

Previous studies have suggested that yeast strains lacking the Ca(2+)-ATPase Pmr1p are unable to maintain an adequate level of Ca(2+) within the Golgi apparatus. It is thought that this compartmental store depletion induces a signal that causes an increased rate of Ca(2+) uptake and accumulation in a manner similar to the capacitative Ca(2+) entry (CCE) response in non-excitable mammalian cells. To explore this model further, we examined cellular Ca(2+) uptake and accumulation in a pmr1Delta strain grown in the presence of a reduced level of divalent cations. We found that the level of Ca(2+) uptake and accumulation in a pmr1Delta strain increased as the concentration of divalent cations in the growth medium decreased. These results are inconsistent with a model in which cellular Ca(2+) uptake and accumulation are determined solely by the depletion of Ca(2+) in an intracellular compartment. Instead, our results suggest that a second regulatory mechanism couples cellular Ca(2+) uptake to the availability of Ca(2+) in the extracellular environment. Furthermore, we found that various conditions that increase the level of cytosolic Ca(2+) correlate with vacuolar fragmentation in wild-type (WT), pmr1Delta and pmr1Delta/pmc1Delta yeast strains. This suggests that vacuolar fragmentation might function as a normal physiological response to Ca(2+) stress that increases the vacuolar surface/volume ratio, thereby maximizing the sequestration of this important signaling molecule.