Casamayor A, Serrano R, Platara M, Casado C, Ruiz A, Arino J

Alkaline pH stress invokes in S. cerevisiae a potent and fast transcriptional response that includes many genes repressed by glucose. Certain mutants in the glucose-sensing and response pathways, such as those lacking the Snf1 kinase, are sensitive to alkalinisation. We show that addition of glucose to the medium improves growth ...

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of wild type cells at high pH, fully abolish the snf1 alkali-sensitive phenotype and attenuates high pH-induced Snf1 phosphorylation at Thr210. Lack of Elm1, one of the three upstream Snf1 kinases (Tos3, Elm1 and Sak1), markedly increases alkali sensitivity, whereas the phenotype of the triple mutant tos3 elm1 sak1 is even stronger than that of snf1 cells and it is poorly rescued by glucose supplementation. DNA microarray analysis reveals that about 75% of genes induced at short term by high pH are also induced by glucose scarcity. Snf1 mediates, in full or in part, the activation of a significant subset (38%) of short-term alkali-induced genes, including those coding high-affinity hexose transporters and phosphorylating enzymes. Induction of genes encoding enzymes involved in glycogen (but not trehalose) metabolism is largely dependent of the presence of Snf1. Therefore, the function of Snf1 in adaptation to glucose scarcity appears crucial for alkaline pH tolerance. Incorporation of micromolar amounts of iron and copper to a glucose-supplemented medium result in an additive effect and allows near normal growth at high pH, thus indicating that these three nutrients are key limiting factors for growth in an alkaline environment.

Date: Feb. 28, 2012

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