Modulation of Yeast Alkaline Cation Tolerance by Ypi1 Requires Calcineurin.

Ypi1 was discovered as an essential protein able to act as a regulatory subunit of the Saccharomyces cerevisiae type 1 protein phosphatase Glc7 and to play a key role in mitosis. We show here that partial depletion of Ypi1 causes lithium sensitivity, and that high levels of this protein confer ...
a lithium-tolerant phenotype to yeast cells. Remarkably, this phenotype was independent of the role of Ypi1 as a Glc7 regulatory subunit. Lithium tolerance in cells overexpressing Ypi1 was caused by a combination of increased efflux of lithium, mediated by augmented expression of the alkaline cation ATPase ENA1, and decreased lithium influx through the Trk1,2 high-affinity potassium transporters. Deletion of CNB1, encoding the regulatory subunit of the calcineurin phosphatase, blocked Ypi1-induced expression of ENA1, normalized Li(+) fluxes, and abolished the Li(+) hypertolerant phenotype of Ypi1-overexpressing cells. These results point out to a complex role of Ypi1 on the regulation of cation homeostasis, largely mediated by the calcineurin phosphatase.
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Date: Feb. 23, 2012
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