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Eukaryotic Cell, August 2005, p. 1375-1386, Vol. 4, No. 8
1535-9778/05/$08.00+0     doi:10.1128/EC.4.8.1375-1386.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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

Sandra Claret, Xavier Gatti, François Doignon, Didier Thoraval,* and Marc Crouzet

Laboratoire de Biologie Moléculaire et de Séquençage, Institut de Biochimie et Génétique Cellulaires, UMR CNRS/Université Bordeaux 2 5095, Box 64, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France

Received 11 March 2005/ Accepted 20 May 2005

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 rgd1{Delta} strain is sensitive to low pH, and Rgd1p activates the PKC pathway in an acidic environment. Inactivation of both genes in the double mutant rgd1{Delta} mid2{Delta} strain renders yeast cells unable to survive at low pH as in bck1{Delta} and slt2{Delta} 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 rgd1{Delta} 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.


* Corresponding author. Mailing address: 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. Phone: (33) 5 57 57 47 20. Fax: (33) 5 57 57 47 19. E-mail: thoraval{at}u-bordeaux2.fr.


Eukaryotic Cell, August 2005, p. 1375-1386, Vol. 4, No. 8
1535-9778/05/$08.00+0     doi:10.1128/EC.4.8.1375-1386.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.




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