title: Zds1/Zds2-PP2ACdc55 complex specifies signaling output from Rho1 GTPase.
abstract: Budding yeast Rho1 guanosine triphosphatase (GTPase) plays an essential role in polarized cell growth by regulating cell wall glucan synthesis and actin organization. Upon cell wall damage, Rho1 blocks polarized cell growth and repairs the wounds by activating the cell wall integrity (CWI) Pkc1-mitogen-activated protein kinase (MAPK) pathway. A fundamental question is how active Rho1 promotes distinct signaling outputs under different conditions. Here we identified the Zds1/Zds2-protein phosphatase 2A(Cdc55) (PP2A(Cdc55)) complex as a novel Rho1 effector that regulates Rho1 signaling specificity. Zds1/Zds2-PP2A(Cdc55) promotes polarized growth and cell wall synthesis by inhibiting Rho1 GTPase-activating protein (GAP) Lrg1 but inhibits CWI pathway by stabilizing another Rho1 GAP, Sac7, suggesting that active Rho1 is biased toward cell growth over stress response. Conversely, upon cell wall damage, Pkc1-Mpk1 activity inhibits cortical PP2A(Cdc55), ensuring that Rho1 preferentially activates the CWI pathway for cell wall repair. We propose that PP2A(Cdc55) specifies Rho1 signaling output and that reciprocal antagonism between Rho1-PP2A(Cdc55) and Rho1-Pkc1 explains how only one signaling pathway is robustly activated at a time.
authors.affiliation: Department of Biology and Rosenstiel Basic Biomedical Sciences Research Center, Brandeis University, Waltham, MA 02454.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Jonasson
authors.affiliation: Department of Biology and Rosenstiel Basic Biomedical Sciences Research Center, Brandeis University, Waltham, MA 02454.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rossio
authors.affiliation: Department of Biology and Rosenstiel Basic Biomedical Sciences Research Center, Brandeis University, Waltham, MA 02454.
authors.forename: Riko
authors.initials: R
authors.lastname: Hatakeyama
authors.affiliation: Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa 277-8561, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Abe
authors.affiliation: Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa 277-8561, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ohya
authors.affiliation: Department of Biology and Rosenstiel Basic Biomedical Sciences Research Center, Brandeis University, Waltham, MA 02454 Gunma University Initiative for Advanced Research and Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan satoshi@gunma-u.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshida
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C071246:CDC55 protein, S cerevisiae; D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; C101740:ZDS1 protein, S cerevisiae; C101741:ZDS2 protein, S cerevisiae; D054648:Protein Phosphatase 2; C051302:RHO1 protein, S cerevisiae; D020741:rho GTP-Binding Proteins