Chlamydia Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning

Jordan Wesolowski; Mary M Weber; Agata Nawrotek; Cheryl A Dooley; Mike Calderon; Claudette M St Croix; Ted Hackstadt; Jacqueline Cherfils; Fabienne Paumet

doi:10.1128/mBio.02280-16

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Chlamydia Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning

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Chlamydia Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning

Jordan Wesolowski, Mary M Weber, Agata Nawrotek, Cheryl A Dooley, Mike Calderon, Claudette M St Croix, Ted Hackstadt, Jacqueline Cherfils and Fabienne Paumet

mBio, Vol.8(3), p.e02280-16

05/02/2017

DOI: 10.1128/mBio.02280-16

PMCID: PMC5414008

PMID: 28465429

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Abstract

The intracellular bacterium develops in a parasitic compartment called the inclusion. Posttranslationally modified microtubules encase the inclusion, controlling the positioning of Golgi complex fragments around the inclusion. The molecular mechanisms by which coopts the host cytoskeleton and the Golgi complex to sustain its infectious compartment are unknown. Here, using a genetically modified strain, we discovered that both posttranslationally modified microtubules and Golgi complex positioning around the inclusion are controlled by the chlamydial inclusion protein CT813/CTL0184/InaC and host ARF GTPases. CT813 recruits ARF1 and ARF4 to the inclusion membrane, where they induce posttranslationally modified microtubules. Similarly, both ARF isoforms are required for the repositioning of Golgi complex fragments around the inclusion. We demonstrate that CT813 directly recruits ARF GTPases on the inclusion membrane and plays a pivotal role in their activation. Together, these results reveal that uses CT813 to hijack ARF GTPases to couple posttranslationally modified microtubules and Golgi complex repositioning at the inclusion. is an important cause of morbidity and a significant economic burden in the world. However, how develops its intracellular compartment, the so-called inclusion, is poorly understood. Using genetically engineered mutants, we discovered that the effector protein CT813 recruits and activates host ADP-ribosylation factor 1 (ARF1) and ARF4 to regulate microtubules. In this context, CT813 acts as a molecular platform that induces the posttranslational modification of microtubules around the inclusion. These cages are then used to reposition the Golgi complex during infection and promote the development of the inclusion. This study provides the first evidence that ARF1 and ARF4 play critical roles in controlling posttranslationally modified microtubules around the inclusion and that hijacks this novel function of ARF to reposition the Golgi complex.

Chlamydia trachomatis - genetics

Humans

Bacterial Proteins - genetics

Actins

Chlamydia trachomatis - metabolism

Host-Pathogen Interactions

Microtubules - metabolism

GTP Phosphohydrolases - metabolism

Microtubules - genetics

Inclusion Bodies - microbiology

ADP-Ribosylation Factor 1 - metabolism

Bacterial Proteins - metabolism

Golgi Apparatus - metabolism

Protein Processing, Post-Translational

ADP-Ribosylation Factors - metabolism

HeLa Cells

Golgi Apparatus - ultrastructure

Details

Title: Subtitle: Chlamydia Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning
Creators: Jordan Wesolowski - Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
Mary M Weber - Host-Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA
Agata Nawrotek - Laboratoire de Biologie and Pharmacologie Appliquée, Centre National de la Recherche Scientifique, Ecole Normale Supérieure Paris-Saclay, Cachan, France
Cheryl A Dooley - Host-Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA
Mike Calderon - Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Claudette M St Croix - Center for Biologic Imaging, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Ted Hackstadt - Host-Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA
Jacqueline Cherfils - Laboratoire de Biologie and Pharmacologie Appliquée, Centre National de la Recherche Scientifique, Ecole Normale Supérieure Paris-Saclay, Cachan, France
Fabienne Paumet - Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA Fabienne.Paumet@Jefferson.edu
Resource Type: Journal article
Publication Details: mBio, Vol.8(3), p.e02280-16
DOI: 10.1128/mBio.02280-16
PMID: 28465429
PMCID: PMC5414008
NLM abbreviation: mBio
ISSN: 2161-2129
eISSN: 2150-7511
Grant note: R01 AI073486 / NIAID NIH HHS R01 AI116983 / NIAID NIH HHS R56 AI073486 / NIAID NIH HHS
Language: English
Date published: 05/02/2017
Academic Unit: Molecular Physiology and Biophysics; Microbiology and Immunology
Record Identifier: 9984083891702771

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