Gis4, a New Component of the Ion Homeostasis System in the Yeast Saccharomyces cerevisiae

Abstract

Gis4 is a new component of the system required for acquisition of salt tolerance in Saccharomyces cerevisiae. The gis4⌬ mutant is sensitive to Na ؉ and Li ؉ ions but not to osmotic stress. Genetic evidence suggests that Gis4 mediates its function in salt tolerance, at least partly, together with the Snf1 protein kinase and in parallel with the calcineurin protein phosphatase. When exposed to salt stress, mutants lacking gis4⌬ display a defect in maintaining low intracellular levels of Na ؉ and Li ؉ ions and exporting those ions from the cell. This defect is due to diminished expression of the ENA1 gene, which encodes the Na ؉ and Li ؉ export pump. The protein sequence of Gis4 is poorly conserved and does not reveal any hints to its molecular function. Gis4 is enriched at the cell surface, probably due to C-terminal farnesylation. The CAAX box at the C terminus is required for cell surface localization but does not seem to be strictly essential for the function of Gis4 in salt tolerance. Gis4 and Snf1 seem to share functions in the control of ion homeostasis and ENA1 expression but not in glucose derepression, the best known role of Snf1. Together with additional evidence that links Gis4 genetically and physically to Snf1, it appears that Gis4 may function in a pathway in which Snf1 plays a specific role in controlling ion homeostasis. Hence, it appears that the conserved Snf1 kinase plays roles in different pathways controlling nutrient as well as stress response.

Yeast translational response to high salinity: Global analysis reveals regulation at multiple levels

“…Since none of these genes (BCY1 or TIP41) was translationally affected by the loss of Hog1p, these modes of PKA and TOR signaling regulation are probably Hog1p independent. Interestingly, the TOR, but not the HOG, pathway was shown to be required for resistance to cation toxicity (Crespo et al 2001;Ye et al 2006). Thus, it is possible that some of the HOG-independent regulation includes a response to the cation toxic effect imposed by the sodium ions.…”

Regulation of Snf1 Protein Kinase in Response to Environmental Stress

“…In addition, snf1⌬ mutant cultures show reduced thermotolerance in the stationary phase (13). Snf1 has been shown to affect transcription of stress-responsive genes such as ENA1, encoding Na ϩ -ATPase; the snf1⌬ mutant is defective in induction of ENA1 in response to alkaline or sodium ion stress (25,27). Interestingly, when cells are starved for glucose, Snf1 also promotes induction of ENA1 (26), activates heat shock transcription factor Hsf1 (29, 30), and phosphorylates the stress-responsive transcription factor Msn2, thereby inhibiting its nuclear accumulation (31, 32).…”

The pathway by which the yeast protein kinase Snf1p controls acquisition of sodium tolerance is different from that mediating glucose regulation

“…Mutants lacking ENA1 exhibit hypersensitivity to sodium and lithium (Haro et al, 1991). Transcription of the ENA1 gene is controlled by multiple signalling transduction pathways, such as the HOG pathway Rep et al, 2001), the calcineurin pathway (Hirata et al, 1995;Mendizabal et al, 2001;Mendoza et al, 1994Mendoza et al, , 1996, the TOR pathway (Crespo et al, 2001;Withee et al, 1998), the Rim101p pathway (Lamb & Mitchell, 2003;Platara et al, 2006), the protein kinase A (PKA) pathway (Hirata et al, 1995;Marquez & Serrano, 1996) and the Snf1p glucose repression pathway (Alepuz et al, 1997;Ye et al, 2006). In many instances, transcription factors involved in regulation of ENA1 expression have been identified.…”