The Rho3 and Rho4 small GTPases interact functionally with Wsc1p, a cell surface sensor of the protein kinase C cell-integrity pathway in Saccharomyces cerevisiae.
Rgd1, a GTPase-activating protein, is the only known negative regulator of the Rho3 and Rho4 small GTPases in the yeast Saccharomyces cerevisiae. Rho3p and Rho4p are involved in regulating cell polarity by controlling polarized exocytosis. Co-inactivation of RGD1 and WSC1, which is a cell wall sensor-encoding gene, is lethal. Another plasma membrane sensor, Mid2p, is known to rescue the rgd1Deltawsc1Delta synthetic lethality. It has been proposed that Wsc1p and Mid2p act upstream of the protein kinase C (PKC) pathway to function as mechanosensors of cell wall stress. Analysis of the synthetic lethal phenomenon revealed that production of activated Rho3p and Rho4p leads to lethality in wsc1Delta cells. Inactivation of RHO3 or RHO4 was able to rescue the rgd1Deltawsc1Delta synthetic lethality, supporting the idea that the accumulation of GTP-bound Rho proteins, following loss of Rgd1p, is detrimental if the Wsc1 sensor is absent. In contrast, the genetic interaction between RGD1 and MID2 was not due to an accumulation of GTP-bound Rho proteins. It was proposed that simultaneous inactivation of RGD1 and WSC1 constitutively activates the PKC-mitogen-activated protein kinase (MAP kinase) pathway. Moreover, it was shown that the activity of this pathway was not involved in the synthetic lethal interaction, which suggests the existence of another mechanism. Consistent with this idea, it was found that perturbations in Rho3-mediated polarized exocytosis specifically impair the abundance and processing of Wsc1 and Mid2 proteins. Hence, it is proposed that Wsc1p participates in the regulation of a Rho3/4-dependent cellular mechanism, and that this is distinct from the role of Wsc1p in the PKC-MAP kinase pathway.
Fernandes
Helder
H
Laboratoire de Biologie Moléculaire et de Séquençage, Institut de Biochimie et Génétique Cellulaires, UMR Université Victor Segalen Bordeaux 2-CNRS 5095, box 64, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
Roumanie
Olivier
O
Laboratoire de Biologie Moléculaire et de Séquençage, Institut de Biochimie et Génétique Cellulaires, UMR Université Victor Segalen Bordeaux 2-CNRS 5095, box 64, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
Claret
Sandra
S
Laboratoire de Biologie Moléculaire et de Séquençage, Institut de Biochimie et Génétique Cellulaires, UMR Université Victor Segalen Bordeaux 2-CNRS 5095, box 64, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
Gatti
Xavier
X
Laboratoire de Biologie Moléculaire et de Séquençage, Institut de Biochimie et Génétique Cellulaires, UMR Université Victor Segalen Bordeaux 2-CNRS 5095, box 64, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
Thoraval
Didier
D
Laboratoire de Biologie Moléculaire et de Séquençage, Institut de Biochimie et Génétique Cellulaires, UMR Université Victor Segalen Bordeaux 2-CNRS 5095, box 64, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
Doignon
François
F
Laboratoire de Biologie Moléculaire et de Séquençage, Institut de Biochimie et Génétique Cellulaires, UMR Université Victor Segalen Bordeaux 2-CNRS 5095, box 64, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
Crouzet
Marc
M
Laboratoire de Biologie Moléculaire et de Séquençage, Institut de Biochimie et Génétique Cellulaires, UMR Université Victor Segalen Bordeaux 2-CNRS 5095, box 64, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
D019204:GTP-Binding Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D018869:Heat-Shock Response; D008565:Membrane Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D008565:Membrane Proteins; C119383:SLG1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D019204:GTP-Binding Proteins; C074647:RHO3 protein, S cerevisiae; C074648:RHO4 protein, S cerevisiae; D020741:rho GTP-Binding Proteins