title: The Rgd1p Rho GTPase-activating protein and the Mid2p cell wall sensor are required at low pH for protein kinase C pathway activation and cell survival in Saccharomyces cerevisiae.
abstract: The protein kinase C (PKC) pathway is involved in the maintenance of cell shape and cell integrity in Saccharomyces cerevisiae. Here, we show that this pathway mediates tolerance to low pH and that the Bck1 and Slt2 proteins belonging to the mitogen-activated protein kinase cascade are essential for cell survival at low pH. The PKC pathway is activated during acidification of the extracellular environment, and this activation depends mainly on the Mid2p cell wall sensor. Rgd1p, which encodes a Rho GTPase-activating protein for the small G proteins Rho3p and Rho4p, also plays a role in low-pH response. The rgd1Delta strain is sensitive to low pH, and Rgd1p activates the PKC pathway in an acidic environment. Inactivation of both genes in the double mutant rgd1Delta mid2Delta strain renders yeast cells unable to survive at low pH as in bck1Delta and slt2Delta strains. Our data provide evidence for the existence of two distinct ways, one involving Mid2p and the other involving Rgd1p, with both converging to the cell integrity pathway to mediate low-pH tolerance in Saccharomyces cerevisiae. Nevertheless, even if Rgd1p acts on the PKC pathway, it seems that its mediating action on low-pH tolerance is not limited to this pathway. As the Mid2p amount plays a role in rgd1Delta sensitivity to low pH, Mid2p seems to act more like a molecular rheostat, controlling the level of PKC pathway activity and thus allowing phenotypical expression of RGD1 inactivation.
authors.affiliation: Laboratoire de Biologie Moléculaire et de Séquençage, Institut de Biochimie et Génétique Cellulaires, UMR CNRS/Université Bordeaux 2, 5095, boite 64, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Claret
authors.forename: Xavier
authors.initials: X
authors.lastname: Gatti
authors.forename: François
authors.initials: F
authors.lastname: Doignon
authors.forename: Didier
authors.initials: D
authors.lastname: Thoraval
authors.forename: Marc
authors.initials: M
authors.lastname: Crouzet
mesh_terms: D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival; D002473:Cell Wall; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D006863:Hydrogen-Ion Concentration; D047908:Intracellular Signaling Peptides and Proteins; D026161:MADS Domain Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013489:Suppression, Genetic / Q000235:genetics; D013696:Temperature; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; D026161:MADS Domain Proteins; C091625:MID2 protein, S cerevisiae; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C499369:PST1 protein, S cerevisiae; C449479:RGD1 protein, S cerevisiae; C095725:RLM1 protein, S cerevisiae; C119383:SLG1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C085379:rho GTPase-activating protein; C072075:BCK1 protein, S cerevisiae; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C072724:SLT2 protein, S cerevisiae; D020929:Mitogen-Activated Protein Kinase Kinases