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Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial protease

Chlamydiae replicate in a vacuole within epithelial cells and commonly induce cell damage and a deleterious inflammatory response of unknown molecular pathogenesis. The chlamydial protease-like activity factor (CPAF) translocates from the vacuole to the cytosol, where it cleaves several cellular pro...

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Autores principales: Paschen, Stefan A., Christian, Jan G., Vier, Juliane, Schmidt, Franziska, Walch, Axel, Ojcius, David M., Häcker, Georg
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2447887/
https://www.ncbi.nlm.nih.gov/pubmed/18625845
http://dx.doi.org/10.1083/jcb.200804023
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author Paschen, Stefan A.
Christian, Jan G.
Vier, Juliane
Schmidt, Franziska
Walch, Axel
Ojcius, David M.
Häcker, Georg
author_facet Paschen, Stefan A.
Christian, Jan G.
Vier, Juliane
Schmidt, Franziska
Walch, Axel
Ojcius, David M.
Häcker, Georg
author_sort Paschen, Stefan A.
collection PubMed
description Chlamydiae replicate in a vacuole within epithelial cells and commonly induce cell damage and a deleterious inflammatory response of unknown molecular pathogenesis. The chlamydial protease-like activity factor (CPAF) translocates from the vacuole to the cytosol, where it cleaves several cellular proteins. CPAF is synthesized as an inactive precursor that is processed and activated during infection. Here, we show that CPAF can be activated in uninfected cells by experimentally induced oligomerization, reminiscent of the activation mode of initiator caspases. CPAF activity induces proteolysis of cellular substrates including two novel targets, cyclin B1 and PARP, and indirectly results in the processing of pro-apoptotic BH3-only proteins. CPAF activation induces striking morphological changes in the cell and, later, cell death. Biochemical and ultrastructural analysis of the cell death pathway identify the mechanism of cell death as nonapoptotic. Active CPAF in uninfected human cells thus mimics many features of chlamydial infection, implicating CPAF as a major factor of chlamydial pathogenicity, Chlamydia-associated cell damage, and inflammation.
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spelling pubmed-24478872009-01-14 Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial protease Paschen, Stefan A. Christian, Jan G. Vier, Juliane Schmidt, Franziska Walch, Axel Ojcius, David M. Häcker, Georg J Cell Biol Research Articles Chlamydiae replicate in a vacuole within epithelial cells and commonly induce cell damage and a deleterious inflammatory response of unknown molecular pathogenesis. The chlamydial protease-like activity factor (CPAF) translocates from the vacuole to the cytosol, where it cleaves several cellular proteins. CPAF is synthesized as an inactive precursor that is processed and activated during infection. Here, we show that CPAF can be activated in uninfected cells by experimentally induced oligomerization, reminiscent of the activation mode of initiator caspases. CPAF activity induces proteolysis of cellular substrates including two novel targets, cyclin B1 and PARP, and indirectly results in the processing of pro-apoptotic BH3-only proteins. CPAF activation induces striking morphological changes in the cell and, later, cell death. Biochemical and ultrastructural analysis of the cell death pathway identify the mechanism of cell death as nonapoptotic. Active CPAF in uninfected human cells thus mimics many features of chlamydial infection, implicating CPAF as a major factor of chlamydial pathogenicity, Chlamydia-associated cell damage, and inflammation. The Rockefeller University Press 2008-07-14 /pmc/articles/PMC2447887/ /pubmed/18625845 http://dx.doi.org/10.1083/jcb.200804023 Text en © 2008 Paschen 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.jcb.org/misc/terms.shtml). 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 Research Articles
Paschen, Stefan A.
Christian, Jan G.
Vier, Juliane
Schmidt, Franziska
Walch, Axel
Ojcius, David M.
Häcker, Georg
Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial protease
title Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial protease
title_full Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial protease
title_fullStr Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial protease
title_full_unstemmed Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial protease
title_short Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial protease
title_sort cytopathicity of chlamydia is largely reproduced by expression of a single chlamydial protease
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2447887/
https://www.ncbi.nlm.nih.gov/pubmed/18625845
http://dx.doi.org/10.1083/jcb.200804023
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