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

Erin M Jonasson; Valentina Rossio; Riko Hatakeyama; Mitsuhiro Abe; Yoshikazu Ohya; Satoshi Yoshida

doi:10.1083/jcb.201508119

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

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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 language	English
Pages (from-to)	51-61
Number of pages	11
Journal	Journal of Cell Biology
Volume	212
Issue number	1
DOIs	https://doi.org/10.1083/jcb.201508119
Publication status	Published - 4 Jan 2016

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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10.1083/jcb.201508119Licence: CC BY-NC-SA

Jonasson_etal_JCB_Zds1Zds2_PP2ACdc55_Complex_VOR
© 2016 Jonasson et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
Final published version, 2.69 MBLicence: CC BY-NC-SA

Riko Hatakeyama
Person: Academic

Cite this

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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. ",

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",

author = "Jonasson, {Erin M} and Valentina Rossio and Riko Hatakeyama and Mitsuhiro Abe and Yoshikazu Ohya and Satoshi Yoshida",

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).",

year = "2016",

month = jan,

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doi = "10.1083/jcb.201508119",

language = "English",

volume = "212",

pages = "51--61",

journal = "Journal of Cell Biology",

issn = "0021-9525",

publisher = "Rockefeller University Press",

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T1 - Zds1/Zds2-PP2ACdc55 complex specifies signaling output from Rho1 GTPase

AU - Jonasson, Erin M

AU - Rossio, Valentina

AU - Hatakeyama, Riko

AU - Abe, Mitsuhiro

AU - Ohya, Yoshikazu

AU - Yoshida, Satoshi

N1 - 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).

PY - 2016/1/4

Y1 - 2016/1/4

N2 - 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.

AB - 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.

KW - Adaptor Proteins, Signal Transducing/metabolism

KW - Cell Cycle Proteins/metabolism

KW - Protein Phosphatase 2/metabolism

KW - Saccharomyces cerevisiae/enzymology

KW - Saccharomyces cerevisiae Proteins/metabolism

KW - Signal Transduction

KW - rho GTP-Binding Proteins/metabolism

U2 - 10.1083/jcb.201508119

DO - 10.1083/jcb.201508119

M3 - Article

C2 - 26728856

SN - 0021-9525

VL - 212

SP - 51

EP - 61

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 1

ER -

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

Abstract

Bibliographical note

Keywords

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Riko Hatakeyama

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