<italic toggle="yes">Chlamydia</italic> Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning
ABSTRACT The intracellular bacterium Chlamydia trachomatis 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 Chlamydi...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2017-07-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02280-16 |
| _version_ | 1830288324642734080 |
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| author | Jordan Wesolowski Mary M. Weber Agata Nawrotek Cheryl A. Dooley Mike Calderon Claudette M. St. Croix Ted Hackstadt Jacqueline Cherfils Fabienne Paumet |
| author_facet | Jordan Wesolowski Mary M. Weber Agata Nawrotek Cheryl A. Dooley Mike Calderon Claudette M. St. Croix Ted Hackstadt Jacqueline Cherfils Fabienne Paumet |
| author_sort | Jordan Wesolowski |
| collection | DOAJ |
| description | ABSTRACT The intracellular bacterium Chlamydia trachomatis 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 Chlamydia coopts the host cytoskeleton and the Golgi complex to sustain its infectious compartment are unknown. Here, using a genetically modified Chlamydia 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 Chlamydia uses CT813 to hijack ARF GTPases to couple posttranslationally modified microtubules and Golgi complex repositioning at the inclusion. IMPORTANCE Chlamydia trachomatis is an important cause of morbidity and a significant economic burden in the world. However, how Chlamydia develops its intracellular compartment, the so-called inclusion, is poorly understood. Using genetically engineered Chlamydia 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 Chlamydia trachomatis hijacks this novel function of ARF to reposition the Golgi complex. |
| first_indexed | 2024-12-19T04:33:16Z |
| format | Article |
| id | doaj.art-1b0aa9e0ba83433dbf1e26bc29d92500 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T04:33:16Z |
| publishDate | 2017-07-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-1b0aa9e0ba83433dbf1e26bc29d925002022-12-21T20:35:49ZengAmerican Society for MicrobiologymBio2150-75112017-07-018310.1128/mBio.02280-16<italic toggle="yes">Chlamydia</italic> Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex PositioningJordan Wesolowski0Mary M. Weber1Agata Nawrotek2Cheryl A. Dooley3Mike Calderon4Claudette M. St. Croix5Ted Hackstadt6Jacqueline Cherfils7Fabienne Paumet8Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania, USAHost-Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USALaboratoire de Biologie and Pharmacologie Appliquée, Centre National de la Recherche Scientifique, Ecole Normale Supérieure Paris-Saclay, Cachan, FranceHost-Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USACenter for Biologic Imaging, University of Pittsburgh, Pittsburgh, Pennsylvania, USACenter for Biologic Imaging, University of Pittsburgh, Pittsburgh, Pennsylvania, USAHost-Parasite Interactions Section, Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USALaboratoire de Biologie and Pharmacologie Appliquée, Centre National de la Recherche Scientifique, Ecole Normale Supérieure Paris-Saclay, Cachan, FranceDepartment of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania, USAABSTRACT The intracellular bacterium Chlamydia trachomatis 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 Chlamydia coopts the host cytoskeleton and the Golgi complex to sustain its infectious compartment are unknown. Here, using a genetically modified Chlamydia 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 Chlamydia uses CT813 to hijack ARF GTPases to couple posttranslationally modified microtubules and Golgi complex repositioning at the inclusion. IMPORTANCE Chlamydia trachomatis is an important cause of morbidity and a significant economic burden in the world. However, how Chlamydia develops its intracellular compartment, the so-called inclusion, is poorly understood. Using genetically engineered Chlamydia 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 Chlamydia trachomatis hijacks this novel function of ARF to reposition the Golgi complex.https://journals.asm.org/doi/10.1128/mBio.02280-16ARF GTPaseactinCT813Chlamydia trachomatisGolgi complexinclusion protein |
| spellingShingle | Jordan Wesolowski Mary M. Weber Agata Nawrotek Cheryl A. Dooley Mike Calderon Claudette M. St. Croix Ted Hackstadt Jacqueline Cherfils Fabienne Paumet <italic toggle="yes">Chlamydia</italic> Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning mBio ARF GTPase actin CT813 Chlamydia trachomatis Golgi complex inclusion protein |
| title | <italic toggle="yes">Chlamydia</italic> Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning |
| title_full | <italic toggle="yes">Chlamydia</italic> Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning |
| title_fullStr | <italic toggle="yes">Chlamydia</italic> Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning |
| title_full_unstemmed | <italic toggle="yes">Chlamydia</italic> Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning |
| title_short | <italic toggle="yes">Chlamydia</italic> Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning |
| title_sort | italic toggle yes chlamydia italic hijacks arf gtpases to coordinate microtubule posttranslational modifications and golgi complex positioning |
| topic | ARF GTPase actin CT813 Chlamydia trachomatis Golgi complex inclusion protein |
| url | https://journals.asm.org/doi/10.1128/mBio.02280-16 |
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