A role for the non-phosphorylated form of yeast Snf1: tolerance to toxic cations and activation of potassium transport.

The Snf1/AMP-activated protein kinases play a key role in stress responses of eukaryotic cells. In the yeast Saccharomyces cerevisiae Snf1 is regulated by glucose depletion, which triggers its phosphorylation at Thr210 and concomitant increase in activity. Activated yeast Snf1 is required for the metabolic changes allowing starvation tolerance and utilization of alternative carbon sources. We now report a function for the non-activated form of Snf1: the regulation of the Trk high-affinity potassium transporter, encoded by the TRK1 and TRK2 genes. A snf1Delta strain is hypersensitive in high-glucose medium to different toxic cations, suggesting a hyperpolarization of the plasma membrane driving increased cation uptake. This phenotype is suppressed by the TRK1 and HAL5 genes in high-copy number consistent with a defect in K(+) uptake mediated by the Trk system. Accordingly, Rb(+) uptake and intracellular K(+) measurements indicate that snf1Delta is unable to fully activate K(+) import. Genetic analysis suggests that the weak kinase activity of the non-phosphorylated form of Snf1 activates Trk in glucose-metabolizing yeast cells. The effect of Snf1 on Trk is probably indirect and could be mediated by the Sip4 transcriptional activator.