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ATF6β is a host cellular target of the Toxoplasma gondii virulence factor ROP18
The ROP18 kinase has been identified as a key virulence determinant conferring a high mortality phenotype characteristic of type I Toxoplasma gondii strains. This major effector molecule is secreted by the rhoptries into the host cells during invasion; however, the molecular mechanisms by which this...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135360/ https://www.ncbi.nlm.nih.gov/pubmed/21670204 http://dx.doi.org/10.1084/jem.20101660 |
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author | Yamamoto, Masahiro Ma, Ji Su Mueller, Christina Kamiyama, Naganori Saiga, Hiroyuki Kubo, Emi Kimura, Taishi Okamoto, Toru Okuyama, Megumi Kayama, Hisako Nagamune, Kisaburo Takashima, Seiji Matsuura, Yoshiharu Soldati-Favre, Dominique Takeda, Kiyoshi |
author_facet | Yamamoto, Masahiro Ma, Ji Su Mueller, Christina Kamiyama, Naganori Saiga, Hiroyuki Kubo, Emi Kimura, Taishi Okamoto, Toru Okuyama, Megumi Kayama, Hisako Nagamune, Kisaburo Takashima, Seiji Matsuura, Yoshiharu Soldati-Favre, Dominique Takeda, Kiyoshi |
author_sort | Yamamoto, Masahiro |
collection | PubMed |
description | The ROP18 kinase has been identified as a key virulence determinant conferring a high mortality phenotype characteristic of type I Toxoplasma gondii strains. This major effector molecule is secreted by the rhoptries into the host cells during invasion; however, the molecular mechanisms by which this kinase exerts its pathogenic action remain poorly understood. In this study, we show that ROP18 targets the host endoplasmic reticulum–bound transcription factor ATF6β. Disruption of the ROP18 gene severely impairs acute toxoplasmosis by the type I RH strain. Because another virulence factor ROP16 kinase modulates immune responses through its N-terminal portion, we focus on the role of the N terminus of ROP18 in the subversion of host cellular functions. The N-terminal extension of ROP18 contributes to ATF6β-dependent pathogenicity by interacting with ATF6β and destabilizing it. The kinase activity of ROP18 is essential for proteasome-dependent degradation of ATF6β and for parasite virulence. Consistent with a key role for ATF6β in resistance against this intracellular pathogen, ATF6β-deficient mice exhibit a high susceptibility to infection by ROP18-deficient parasites. The results reveal that interference with ATF6β-dependent immune responses is a novel pathogenic mechanism induced by ROP18. |
format | Online Article Text |
id | pubmed-3135360 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-31353602012-01-04 ATF6β is a host cellular target of the Toxoplasma gondii virulence factor ROP18 Yamamoto, Masahiro Ma, Ji Su Mueller, Christina Kamiyama, Naganori Saiga, Hiroyuki Kubo, Emi Kimura, Taishi Okamoto, Toru Okuyama, Megumi Kayama, Hisako Nagamune, Kisaburo Takashima, Seiji Matsuura, Yoshiharu Soldati-Favre, Dominique Takeda, Kiyoshi J Exp Med Article The ROP18 kinase has been identified as a key virulence determinant conferring a high mortality phenotype characteristic of type I Toxoplasma gondii strains. This major effector molecule is secreted by the rhoptries into the host cells during invasion; however, the molecular mechanisms by which this kinase exerts its pathogenic action remain poorly understood. In this study, we show that ROP18 targets the host endoplasmic reticulum–bound transcription factor ATF6β. Disruption of the ROP18 gene severely impairs acute toxoplasmosis by the type I RH strain. Because another virulence factor ROP16 kinase modulates immune responses through its N-terminal portion, we focus on the role of the N terminus of ROP18 in the subversion of host cellular functions. The N-terminal extension of ROP18 contributes to ATF6β-dependent pathogenicity by interacting with ATF6β and destabilizing it. The kinase activity of ROP18 is essential for proteasome-dependent degradation of ATF6β and for parasite virulence. Consistent with a key role for ATF6β in resistance against this intracellular pathogen, ATF6β-deficient mice exhibit a high susceptibility to infection by ROP18-deficient parasites. The results reveal that interference with ATF6β-dependent immune responses is a novel pathogenic mechanism induced by ROP18. The Rockefeller University Press 2011-07-04 /pmc/articles/PMC3135360/ /pubmed/21670204 http://dx.doi.org/10.1084/jem.20101660 Text en © 2011 Yamamoto 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/). |
spellingShingle | Article Yamamoto, Masahiro Ma, Ji Su Mueller, Christina Kamiyama, Naganori Saiga, Hiroyuki Kubo, Emi Kimura, Taishi Okamoto, Toru Okuyama, Megumi Kayama, Hisako Nagamune, Kisaburo Takashima, Seiji Matsuura, Yoshiharu Soldati-Favre, Dominique Takeda, Kiyoshi ATF6β is a host cellular target of the Toxoplasma gondii virulence factor ROP18 |
title | ATF6β is a host cellular target of the Toxoplasma gondii virulence factor ROP18 |
title_full | ATF6β is a host cellular target of the Toxoplasma gondii virulence factor ROP18 |
title_fullStr | ATF6β is a host cellular target of the Toxoplasma gondii virulence factor ROP18 |
title_full_unstemmed | ATF6β is a host cellular target of the Toxoplasma gondii virulence factor ROP18 |
title_short | ATF6β is a host cellular target of the Toxoplasma gondii virulence factor ROP18 |
title_sort | atf6β is a host cellular target of the toxoplasma gondii virulence factor rop18 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135360/ https://www.ncbi.nlm.nih.gov/pubmed/21670204 http://dx.doi.org/10.1084/jem.20101660 |
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