ATC1/LIC4, previously identified as a suppressor of the Li+-sensitive phenotype of calcineurin mutants, was also identified as a suppressor of the hygromycin B-sensitive phenotype of strains lacking the G protein gene, ARL1. Although loss of ARL1 confers several phenotypes, including sensitivity to hygromycin B and Li+, reduced influx of K+, and increased secretion of carboxypeptidase Y (CPY), loss of A TO was without effect by these and other measures. However, loss of A TO in an ar11 background exacerbated ion sensitivities, although not the CPY phenotype. Moreover, overexpression of A TO in an ar11 background partially suppressed ion sensitivities, but not the CPY phenotype. Additionally, expression of ENA1, the Na+/Li+ efflux ATPase, and activated calcineurin. but not normal calcineurin, suppressed the Li+-sensitive phenotype of the ar11 atc1 double mutant. These results show ARL1 and ATC1 interact to control intracellular ion levels, but ATC1 has little influence on other functions of ARL1. (C) 2004 Elsevier Inc. All rights reserved.