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Activation of Ran GTPase by a Legionella effector promotes microtubule polymerization, pathogen vacuole motility and infection

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Activation of Ran GTPase by a Legionella effector promotes microtubule polymerization, pathogen vacuole motility and infection. / Rothmeier, Eva; Pfaffinger, Gudrun; Hoffmann, Christine; Harrison, Christopher F; Grabmayr, Heinrich; Repnik, Urska; Hannemann, Mandy; Wölke, Stefan; Bausch, Andreas; Griffiths, Gareth; Müller-Taubenberger, Annette; Itzen, Aymelt; Hilbi, Hubert.

in: PLOS PATHOG, Jahrgang 9, Nr. 9, 09.2013, S. e1003598.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Rothmeier, E, Pfaffinger, G, Hoffmann, C, Harrison, CF, Grabmayr, H, Repnik, U, Hannemann, M, Wölke, S, Bausch, A, Griffiths, G, Müller-Taubenberger, A, Itzen, A & Hilbi, H 2013, 'Activation of Ran GTPase by a Legionella effector promotes microtubule polymerization, pathogen vacuole motility and infection', PLOS PATHOG, Jg. 9, Nr. 9, S. e1003598. https://doi.org/10.1371/journal.ppat.1003598

APA

Rothmeier, E., Pfaffinger, G., Hoffmann, C., Harrison, C. F., Grabmayr, H., Repnik, U., Hannemann, M., Wölke, S., Bausch, A., Griffiths, G., Müller-Taubenberger, A., Itzen, A., & Hilbi, H. (2013). Activation of Ran GTPase by a Legionella effector promotes microtubule polymerization, pathogen vacuole motility and infection. PLOS PATHOG, 9(9), e1003598. https://doi.org/10.1371/journal.ppat.1003598

Vancouver

Rothmeier E, Pfaffinger G, Hoffmann C, Harrison CF, Grabmayr H, Repnik U et al. Activation of Ran GTPase by a Legionella effector promotes microtubule polymerization, pathogen vacuole motility and infection. PLOS PATHOG. 2013 Sep;9(9):e1003598. https://doi.org/10.1371/journal.ppat.1003598

Bibtex

@article{95bac8d44ad44e91bbc88a43e2073b23,
title = "Activation of Ran GTPase by a Legionella effector promotes microtubule polymerization, pathogen vacuole motility and infection",
abstract = "The causative agent of Legionnaires' disease, Legionella pneumophila, uses the Icm/Dot type IV secretion system (T4SS) to form in phagocytes a distinct {"}Legionella-containing vacuole{"} (LCV), which intercepts endosomal and secretory vesicle trafficking. Proteomics revealed the presence of the small GTPase Ran and its effector RanBP1 on purified LCVs. Here we validate that Ran and RanBP1 localize to LCVs and promote intracellular growth of L. pneumophila. Moreover, the L. pneumophila protein LegG1, which contains putative RCC1 Ran guanine nucleotide exchange factor (GEF) domains, accumulates on LCVs in an Icm/Dot-dependent manner. L. pneumophila wild-type bacteria, but not strains lacking LegG1 or a functional Icm/Dot T4SS, activate Ran on LCVs, while purified LegG1 produces active Ran(GTP) in cell lysates. L. pneumophila lacking legG1 is compromised for intracellular growth in macrophages and amoebae, yet is as cytotoxic as the wild-type strain. A downstream effect of LegG1 is to stabilize microtubules, as revealed by conventional and stimulated emission depletion (STED) fluorescence microscopy, subcellular fractionation and Western blot, or by microbial microinjection through the T3SS of a Yersinia strain lacking endogenous effectors. Real-time fluorescence imaging indicates that LCVs harboring wild-type L. pneumophila rapidly move along microtubules, while LCVs harboring ΔlegG1 mutant bacteria are stalled. Together, our results demonstrate that Ran activation and RanBP1 promote LCV formation, and the Icm/Dot substrate LegG1 functions as a bacterial Ran activator, which localizes to LCVs and promotes microtubule stabilization, LCV motility as well as intracellular replication of L. pneumophila. ",
keywords = "Animals, Bacterial Proteins, Cell Line, Enzyme Activation, GTPase-Activating Proteins, Gene Silencing, Humans, Legionella pneumophila, Legionnaires' Disease, Macrophages, Mice, Microtubule Proteins, Microtubules, Mutation, Phagocytosis, Phagosomes, Polymerization, Protein Stability, Protein Transport, Virus Replication, ran GTP-Binding Protein, Journal Article, Research Support, Non-U.S. Gov't",
author = "Eva Rothmeier and Gudrun Pfaffinger and Christine Hoffmann and Harrison, {Christopher F} and Heinrich Grabmayr and Urska Repnik and Mandy Hannemann and Stefan W{\"o}lke and Andreas Bausch and Gareth Griffiths and Annette M{\"u}ller-Taubenberger and Aymelt Itzen and Hubert Hilbi",
year = "2013",
month = sep,
doi = "10.1371/journal.ppat.1003598",
language = "English",
volume = "9",
pages = "e1003598",
journal = "PLOS PATHOG",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "9",

}

RIS

TY - JOUR

T1 - Activation of Ran GTPase by a Legionella effector promotes microtubule polymerization, pathogen vacuole motility and infection

AU - Rothmeier, Eva

AU - Pfaffinger, Gudrun

AU - Hoffmann, Christine

AU - Harrison, Christopher F

AU - Grabmayr, Heinrich

AU - Repnik, Urska

AU - Hannemann, Mandy

AU - Wölke, Stefan

AU - Bausch, Andreas

AU - Griffiths, Gareth

AU - Müller-Taubenberger, Annette

AU - Itzen, Aymelt

AU - Hilbi, Hubert

PY - 2013/9

Y1 - 2013/9

N2 - The causative agent of Legionnaires' disease, Legionella pneumophila, uses the Icm/Dot type IV secretion system (T4SS) to form in phagocytes a distinct "Legionella-containing vacuole" (LCV), which intercepts endosomal and secretory vesicle trafficking. Proteomics revealed the presence of the small GTPase Ran and its effector RanBP1 on purified LCVs. Here we validate that Ran and RanBP1 localize to LCVs and promote intracellular growth of L. pneumophila. Moreover, the L. pneumophila protein LegG1, which contains putative RCC1 Ran guanine nucleotide exchange factor (GEF) domains, accumulates on LCVs in an Icm/Dot-dependent manner. L. pneumophila wild-type bacteria, but not strains lacking LegG1 or a functional Icm/Dot T4SS, activate Ran on LCVs, while purified LegG1 produces active Ran(GTP) in cell lysates. L. pneumophila lacking legG1 is compromised for intracellular growth in macrophages and amoebae, yet is as cytotoxic as the wild-type strain. A downstream effect of LegG1 is to stabilize microtubules, as revealed by conventional and stimulated emission depletion (STED) fluorescence microscopy, subcellular fractionation and Western blot, or by microbial microinjection through the T3SS of a Yersinia strain lacking endogenous effectors. Real-time fluorescence imaging indicates that LCVs harboring wild-type L. pneumophila rapidly move along microtubules, while LCVs harboring ΔlegG1 mutant bacteria are stalled. Together, our results demonstrate that Ran activation and RanBP1 promote LCV formation, and the Icm/Dot substrate LegG1 functions as a bacterial Ran activator, which localizes to LCVs and promotes microtubule stabilization, LCV motility as well as intracellular replication of L. pneumophila.

AB - The causative agent of Legionnaires' disease, Legionella pneumophila, uses the Icm/Dot type IV secretion system (T4SS) to form in phagocytes a distinct "Legionella-containing vacuole" (LCV), which intercepts endosomal and secretory vesicle trafficking. Proteomics revealed the presence of the small GTPase Ran and its effector RanBP1 on purified LCVs. Here we validate that Ran and RanBP1 localize to LCVs and promote intracellular growth of L. pneumophila. Moreover, the L. pneumophila protein LegG1, which contains putative RCC1 Ran guanine nucleotide exchange factor (GEF) domains, accumulates on LCVs in an Icm/Dot-dependent manner. L. pneumophila wild-type bacteria, but not strains lacking LegG1 or a functional Icm/Dot T4SS, activate Ran on LCVs, while purified LegG1 produces active Ran(GTP) in cell lysates. L. pneumophila lacking legG1 is compromised for intracellular growth in macrophages and amoebae, yet is as cytotoxic as the wild-type strain. A downstream effect of LegG1 is to stabilize microtubules, as revealed by conventional and stimulated emission depletion (STED) fluorescence microscopy, subcellular fractionation and Western blot, or by microbial microinjection through the T3SS of a Yersinia strain lacking endogenous effectors. Real-time fluorescence imaging indicates that LCVs harboring wild-type L. pneumophila rapidly move along microtubules, while LCVs harboring ΔlegG1 mutant bacteria are stalled. Together, our results demonstrate that Ran activation and RanBP1 promote LCV formation, and the Icm/Dot substrate LegG1 functions as a bacterial Ran activator, which localizes to LCVs and promotes microtubule stabilization, LCV motility as well as intracellular replication of L. pneumophila.

KW - Animals

KW - Bacterial Proteins

KW - Cell Line

KW - Enzyme Activation

KW - GTPase-Activating Proteins

KW - Gene Silencing

KW - Humans

KW - Legionella pneumophila

KW - Legionnaires' Disease

KW - Macrophages

KW - Mice

KW - Microtubule Proteins

KW - Microtubules

KW - Mutation

KW - Phagocytosis

KW - Phagosomes

KW - Polymerization

KW - Protein Stability

KW - Protein Transport

KW - Virus Replication

KW - ran GTP-Binding Protein

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1371/journal.ppat.1003598

DO - 10.1371/journal.ppat.1003598

M3 - SCORING: Journal article

C2 - 24068924

VL - 9

SP - e1003598

JO - PLOS PATHOG

JF - PLOS PATHOG

SN - 1553-7366

IS - 9

ER -