title: Weak acid and alkali stress regulate phosphatidylinositol bisphosphate synthesis in Saccharomyces cerevisiae.
abstract: Weak organic acids are used as food preservatives to inhibit the growth of spoilage yeasts, including Saccharomyces cerevisiae. Long-term adaptation to weak acids requires the increased expression of the ATP-binding cassette transporter Pdr12p, which catalyses the active efflux of the weak acids from the cytosol; however, very little is known about the signalling events immediately following application of weak acid stress. We have investigated the effects of weak acids on two stress-responsive signalling molecules, PtdIns(3,5)P2 and PtdIns(4,5)P2, which in S. cerevisiae are synthesized by Fab1p and Mss4p respectively. At low extracellular pH, benzoic acid, sorbic acid and acetic acid all cause a transient reduction in PtdIns(3,5)P2 accumulation and a more persistent rise in PtdIns(4,5)P2 levels. The increase in PtdIns(4,5)P2 levels is accompanied by a reorganization of the actin cytoskeleton. However, changes in PtdInsP2 levels are independent of weak acid-induced Pdr12p expression. In contrast, changing the extracellular medium to alkaline pH provokes a prolonged and substantial rise in PtdIns(3,5)P2 levels. As PtdIns(3,5)P2 synthesis is required for correct vacuole acidification, it is possible that levels of this molecule are modulated to maintain intracellular pH homoeostasis in response to weak acid and alkali stresses. In conclusion, we have expanded the repertoire of stress responses that affect PtdInsP2 levels to include weak acid and alkali stresses.
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Mollapour
authors.forename: John P
authors.initials: JP
authors.lastname: Phelan
authors.forename: Stefan H
authors.initials: SH
authors.lastname: Millson
authors.forename: Peter W
authors.initials: PW
authors.lastname: Piper
authors.forename: Frank T
authors.initials: FT
authors.lastname: Cooke
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D000468:Alkalies / Q000494:pharmacology*; D019817:Benzoic Acid / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects; D015966:Gene Expression Regulation, Fungal / Q000235:genetics*; D006863:Hydrogen-Ion Concentration; D009154:Mutation / Q000235:genetics; D018129:Phosphatidylinositol Phosphates / Q000096:biosynthesis*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013011:Sorbic Acid / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D018528:ATP-Binding Cassette Transporters; D000199:Actins; D000468:Alkalies; C472673:Pdr12 protein, S cerevisiae; D018129:Phosphatidylinositol Phosphates; D029701:Saccharomyces cerevisiae Proteins; C106336:phosphatidylinositol 3,5-diphosphate; D019817:Benzoic Acid; C095504:FAB1 protein, S cerevisiae; D017853:Phosphotransferases (Alcohol Group Acceptor); D013011:Sorbic Acid