IDENTIFICATION OF A CALCINEURIN-INDEPENDENT PATHWAY REQUIRED FOR SODIUM-ION STRESS-RESPONSE IN SACCHAROMYCES-CEREVISIAE

The calcium-dependent protein phosphatase calcineurin plays an essenti al role in ion homeostasis in yeast. In this study, we identify a para llel ion stress response pathway that is independent of the calcineuri n signaling pathway. Cells with null alleles in both STD1 and its homo logue, MTH1, manifest numerous phenotypes observed in calcineurin muta nts, including sodium, lithium, manganese, and hydroxyl ion sensitivit y, as well as alpha factor toxicity. Furthermore, increased gene dosag e of STD1 suppresses the ion stress phenotypes in calcineurin mutants and confers halotolerance in wild-type cells. However, Std1p functions in a calcineurin-independent ion stress response pathway, since a std 1 mth1 mutant is FK506 sensitive under conditions of ion stress. Mutat ions in other genes known to regulate gene expression in response to c hanges in glucose concentration, including SNF3, RGT2, and SNF5, also affect cell growth under ion stress conditions. Gene expression studie s indicate that the regulation of HAL1 and PMR2 expression is affected by STD1 gene dosage. Taken together, our data demonstrate that respon se to ion stress requires the participation of both calcineurin-depend ent and -independent pathways.