Zds1/Zds2-PP2ACdc55 complex specifies signaling output from Rho1 GTPase

Erin M Jonasson, Valentina Rossio, Riko Hatakeyama, Mitsuhiro Abe, Yoshikazu Ohya, Satoshi Yoshida* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)
5 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)51-61
Number of pages11
JournalJournal of Cell Biology
Volume212
Issue number1
DOIs
Publication statusPublished - 4 Jan 2016
Externally publishedYes

Bibliographical note

Acknowledgments
We thank David Pellman, John Pringle, Daniel Lew, Masaki Mizunuma, Kenji Irie, and the Yeast Genome Resource Center for yeast strains and plasmids and members of Yoshida Laboratory and Keiko Kono for their support. Multicopy suppressor screening for gef∆ was initiated in the Pellman Laboratory with the help of Didem Ilter.
This research was supported by Sprout grant from Brandeis University (E.M. Jonasson and S. Yoshida), an American-Italian Cancer Foundation Postdoctoral fellowship (V. Rossio), and a Massachusetts Life Sciences Center grant (S. Yoshida).

Keywords

  • Adaptor Proteins, Signal Transducing/metabolism
  • Cell Cycle Proteins/metabolism
  • Protein Phosphatase 2/metabolism
  • Saccharomyces cerevisiae/enzymology
  • Saccharomyces cerevisiae Proteins/metabolism
  • Signal Transduction
  • rho GTP-Binding Proteins/metabolism

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