Pom1 DYRK Regulates Localization of the Rga4 GAP to Ensure Bipolar Activation of Cdc42 in Fission Yeast

Hisashi Tatebe, Kentaro Nakano, Rachel Maximo, Kazuhiro Shiozaki

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

Background: In the fission yeast Schizosaccharomyces pombe, cell growth takes place exclusively at both ends of the cylindrical cell. During this highly polarized growth, microtubules are responsible for the placement of the cell-end marker proteins, the Tea1-Tea4/Wsh3 complex, which recruits the Pom1 DYRK-family protein kinase. Pom1 is required for proper positioning of growth sites, and the Δpom1 mutation brings about monopolar cell growth. Results: Pom1 kinase physically interacts with Rga4, which has a GAP (GTPase-activating protein) domain for Rho-family GTPase. Genetic and biochemical evidence indicates that Rga4 functions as GAP for the Cdc42 GTPase, an evolutionarily conserved regulator of F-actin. CRIB (Cdc42/Rac interactive binding)-GFP microscopy has revealed that GTP-bound, active Cdc42 is concentrated to growing cell ends accompanied by developed F-actin structures, where the Rga4 GAP is excluded. The monopolar Δpom1 mutant fails to eliminate Rga4 from the nongrowing cell end, resulting in monopolar distribution of GTP-Cdc42 to the growing cell end. However, mutational inactivation of Rga4 allows Cdc42 to be active at both ends of Δpom1 cells, suggesting that mislocalization of Rga4 in the Δpom1 mutant contributes to its monopolar phenotype. Conclusions: Pom1 kinase recruited to cell ends by the Tea1-Tea4/Wsh3 complex is essential for proper localization of a GAP for Cdc42, Rga4, which ensures bipolar localization of GTP-bound, active Cdc42. Because of the established role of Cdc42 in F-actin formation, these observations provide a new insight into how the microtubule system achieves localized formation of F-actin to generate cell polarity.

Original languageEnglish (US)
Pages (from-to)322-330
Number of pages9
JournalCurrent Biology
Volume18
Issue number5
DOIs
StatePublished - Mar 11 2008

Fingerprint

GTPase-activating proteins
GTPase-Activating Proteins
Schizosaccharomyces
Schizosaccharomyces pombe
Yeast
Actins
Guanosine Triphosphate
Chemical activation
GTP Phosphohydrolases
Cell growth
actin
Phosphotransferases
cells
guanosinetriphosphatase
microtubules
cell growth
phosphotransferases (kinases)
Protein Kinases
Growth
Microtubules

Keywords

  • CELLBIO
  • CELLCYCLE

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Pom1 DYRK Regulates Localization of the Rga4 GAP to Ensure Bipolar Activation of Cdc42 in Fission Yeast. / Tatebe, Hisashi; Nakano, Kentaro; Maximo, Rachel; Shiozaki, Kazuhiro.

In: Current Biology, Vol. 18, No. 5, 11.03.2008, p. 322-330.

Research output: Contribution to journalArticle

Tatebe, Hisashi ; Nakano, Kentaro ; Maximo, Rachel ; Shiozaki, Kazuhiro. / Pom1 DYRK Regulates Localization of the Rga4 GAP to Ensure Bipolar Activation of Cdc42 in Fission Yeast. In: Current Biology. 2008 ; Vol. 18, No. 5. pp. 322-330.
@article{46d1175c8e8547be9ab1f1c3a61cc32c,
title = "Pom1 DYRK Regulates Localization of the Rga4 GAP to Ensure Bipolar Activation of Cdc42 in Fission Yeast",
abstract = "Background: In the fission yeast Schizosaccharomyces pombe, cell growth takes place exclusively at both ends of the cylindrical cell. During this highly polarized growth, microtubules are responsible for the placement of the cell-end marker proteins, the Tea1-Tea4/Wsh3 complex, which recruits the Pom1 DYRK-family protein kinase. Pom1 is required for proper positioning of growth sites, and the Δpom1 mutation brings about monopolar cell growth. Results: Pom1 kinase physically interacts with Rga4, which has a GAP (GTPase-activating protein) domain for Rho-family GTPase. Genetic and biochemical evidence indicates that Rga4 functions as GAP for the Cdc42 GTPase, an evolutionarily conserved regulator of F-actin. CRIB (Cdc42/Rac interactive binding)-GFP microscopy has revealed that GTP-bound, active Cdc42 is concentrated to growing cell ends accompanied by developed F-actin structures, where the Rga4 GAP is excluded. The monopolar Δpom1 mutant fails to eliminate Rga4 from the nongrowing cell end, resulting in monopolar distribution of GTP-Cdc42 to the growing cell end. However, mutational inactivation of Rga4 allows Cdc42 to be active at both ends of Δpom1 cells, suggesting that mislocalization of Rga4 in the Δpom1 mutant contributes to its monopolar phenotype. Conclusions: Pom1 kinase recruited to cell ends by the Tea1-Tea4/Wsh3 complex is essential for proper localization of a GAP for Cdc42, Rga4, which ensures bipolar localization of GTP-bound, active Cdc42. Because of the established role of Cdc42 in F-actin formation, these observations provide a new insight into how the microtubule system achieves localized formation of F-actin to generate cell polarity.",
keywords = "CELLBIO, CELLCYCLE",
author = "Hisashi Tatebe and Kentaro Nakano and Rachel Maximo and Kazuhiro Shiozaki",
year = "2008",
month = "3",
day = "11",
doi = "10.1016/j.cub.2008.02.005",
language = "English (US)",
volume = "18",
pages = "322--330",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - Pom1 DYRK Regulates Localization of the Rga4 GAP to Ensure Bipolar Activation of Cdc42 in Fission Yeast

AU - Tatebe, Hisashi

AU - Nakano, Kentaro

AU - Maximo, Rachel

AU - Shiozaki, Kazuhiro

PY - 2008/3/11

Y1 - 2008/3/11

N2 - Background: In the fission yeast Schizosaccharomyces pombe, cell growth takes place exclusively at both ends of the cylindrical cell. During this highly polarized growth, microtubules are responsible for the placement of the cell-end marker proteins, the Tea1-Tea4/Wsh3 complex, which recruits the Pom1 DYRK-family protein kinase. Pom1 is required for proper positioning of growth sites, and the Δpom1 mutation brings about monopolar cell growth. Results: Pom1 kinase physically interacts with Rga4, which has a GAP (GTPase-activating protein) domain for Rho-family GTPase. Genetic and biochemical evidence indicates that Rga4 functions as GAP for the Cdc42 GTPase, an evolutionarily conserved regulator of F-actin. CRIB (Cdc42/Rac interactive binding)-GFP microscopy has revealed that GTP-bound, active Cdc42 is concentrated to growing cell ends accompanied by developed F-actin structures, where the Rga4 GAP is excluded. The monopolar Δpom1 mutant fails to eliminate Rga4 from the nongrowing cell end, resulting in monopolar distribution of GTP-Cdc42 to the growing cell end. However, mutational inactivation of Rga4 allows Cdc42 to be active at both ends of Δpom1 cells, suggesting that mislocalization of Rga4 in the Δpom1 mutant contributes to its monopolar phenotype. Conclusions: Pom1 kinase recruited to cell ends by the Tea1-Tea4/Wsh3 complex is essential for proper localization of a GAP for Cdc42, Rga4, which ensures bipolar localization of GTP-bound, active Cdc42. Because of the established role of Cdc42 in F-actin formation, these observations provide a new insight into how the microtubule system achieves localized formation of F-actin to generate cell polarity.

AB - Background: In the fission yeast Schizosaccharomyces pombe, cell growth takes place exclusively at both ends of the cylindrical cell. During this highly polarized growth, microtubules are responsible for the placement of the cell-end marker proteins, the Tea1-Tea4/Wsh3 complex, which recruits the Pom1 DYRK-family protein kinase. Pom1 is required for proper positioning of growth sites, and the Δpom1 mutation brings about monopolar cell growth. Results: Pom1 kinase physically interacts with Rga4, which has a GAP (GTPase-activating protein) domain for Rho-family GTPase. Genetic and biochemical evidence indicates that Rga4 functions as GAP for the Cdc42 GTPase, an evolutionarily conserved regulator of F-actin. CRIB (Cdc42/Rac interactive binding)-GFP microscopy has revealed that GTP-bound, active Cdc42 is concentrated to growing cell ends accompanied by developed F-actin structures, where the Rga4 GAP is excluded. The monopolar Δpom1 mutant fails to eliminate Rga4 from the nongrowing cell end, resulting in monopolar distribution of GTP-Cdc42 to the growing cell end. However, mutational inactivation of Rga4 allows Cdc42 to be active at both ends of Δpom1 cells, suggesting that mislocalization of Rga4 in the Δpom1 mutant contributes to its monopolar phenotype. Conclusions: Pom1 kinase recruited to cell ends by the Tea1-Tea4/Wsh3 complex is essential for proper localization of a GAP for Cdc42, Rga4, which ensures bipolar localization of GTP-bound, active Cdc42. Because of the established role of Cdc42 in F-actin formation, these observations provide a new insight into how the microtubule system achieves localized formation of F-actin to generate cell polarity.

KW - CELLBIO

KW - CELLCYCLE

UR - http://www.scopus.com/inward/record.url?scp=40149109750&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40149109750&partnerID=8YFLogxK

U2 - 10.1016/j.cub.2008.02.005

DO - 10.1016/j.cub.2008.02.005

M3 - Article

VL - 18

SP - 322

EP - 330

JO - Current Biology

JF - Current Biology

SN - 0960-9822

IS - 5

ER -