Cdc1-mediated ion homeostasis is essential for yeast cell growth.

cdc1(ts) mutants were first described to arrest with small buds implicating Cdc1 in bud growth. However, using terminal arrest and reciprocal shift studies with two cdc1(ts) alleles, we have found that Cdc1 is required more generally for cell expansion. Such a role for Cdc1 in cell expansion also explains its involvement in bud growth. To define the role of Cdc1 in cell expansion, we studied suppressors of the cdc1-1(ts) growth defect. Most recessive suppressors fall into 3 distinct groups. Whereas group C suppressors (vps4, vps8, etc) affect vacuolar biogenesis and function, mutants from group A (cos1, cos3, snf7) and group B (cos13, ycr44) exhibit only a subset of the vacuolar defects. Further, group A and B suppressors are synthetic lethal with each other and Ycr44 localizes to vacuolar membrane fractions. These, and other, findings support a model in which the cdc1(ts) growth defect is suppressed in group A and B mutants by the loss of a specific vacuolar function. Although the identity of this vacuolar function is not known, Ca²⁺ uptake studies with group A and B mutants implicate ion homeostasis. Consistent with a model in which the suppressors and Cdc1 coordinately regulate ion homeostasis, mutations in CDC1 disturb cellular Ca²⁺ levels, confer sensitivity to Ca²⁺ and EGTA and exhibit synthetic lethality with mutations implicated in ion homeostasis (vph6, cnb1, hog1). Thus, we propose that Cdc1 is required for cell growth as a result of its role in ion homeostasis.