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E-Cadherin Orthologues as Substrates for the Serine Protease High Temperature Requirement A (HtrA)
Helicobacter pylori (H. pylori) expresses the serine protease and chaperone High temperature requirement A (HtrA) that is involved in periplasmic unfolded protein stress response. Additionally, H. pylori-secreted HtrA directly cleaves the human cell adhesion molecule E-cadherin leading to a local di...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945801/ https://www.ncbi.nlm.nih.gov/pubmed/35327548 http://dx.doi.org/10.3390/biom12030356 |
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author | Bernegger, Sabine Hutterer, Evelyn Zarzecka, Urszula Schmidt, Thomas P. Huemer, Markus Widlroither, Isabella Posselt, Gernot Skorko-Glonek, Joanna Wessler, Silja |
author_facet | Bernegger, Sabine Hutterer, Evelyn Zarzecka, Urszula Schmidt, Thomas P. Huemer, Markus Widlroither, Isabella Posselt, Gernot Skorko-Glonek, Joanna Wessler, Silja |
author_sort | Bernegger, Sabine |
collection | PubMed |
description | Helicobacter pylori (H. pylori) expresses the serine protease and chaperone High temperature requirement A (HtrA) that is involved in periplasmic unfolded protein stress response. Additionally, H. pylori-secreted HtrA directly cleaves the human cell adhesion molecule E-cadherin leading to a local disruption of intercellular adhesions during pathogenesis. HtrA-mediated E-cadherin cleavage has been observed in response to a broad range of pathogens, implying that it is a prevalent mechanism in humans. However, less is known whether E-cadherin orthologues serve as substrates for bacterial HtrA. Here, we compared HtrA-mediated cleavage of human E-cadherin with murine, canine, and simian E-cadherin in vitro and during bacterial infection. We found that HtrA targeted mouse and dog E-cadherin equally well, whereas macaque E-cadherin was less fragmented in vitro. We stably re-expressed orthologous E-cadherin (Cdh1) in a CRISPR/Cas9-mediated cdh1 knockout cell line to investigate E-cadherin shedding upon infection using H. pylori wildtype, an isogenic htrA deletion mutant, or complemented mutants as bacterial paradigms. In Western blot analyses and super-resolution microscopy, we demonstrated that H. pylori efficiently cleaved E-cadherin orthologues in an HtrA-dependent manner. These data extend previous knowledge to HtrA-mediated E-cadherin release in mammals, which may shed new light on bacterial infections in non-human organisms. |
format | Online Article Text |
id | pubmed-8945801 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89458012022-03-25 E-Cadherin Orthologues as Substrates for the Serine Protease High Temperature Requirement A (HtrA) Bernegger, Sabine Hutterer, Evelyn Zarzecka, Urszula Schmidt, Thomas P. Huemer, Markus Widlroither, Isabella Posselt, Gernot Skorko-Glonek, Joanna Wessler, Silja Biomolecules Communication Helicobacter pylori (H. pylori) expresses the serine protease and chaperone High temperature requirement A (HtrA) that is involved in periplasmic unfolded protein stress response. Additionally, H. pylori-secreted HtrA directly cleaves the human cell adhesion molecule E-cadherin leading to a local disruption of intercellular adhesions during pathogenesis. HtrA-mediated E-cadherin cleavage has been observed in response to a broad range of pathogens, implying that it is a prevalent mechanism in humans. However, less is known whether E-cadherin orthologues serve as substrates for bacterial HtrA. Here, we compared HtrA-mediated cleavage of human E-cadherin with murine, canine, and simian E-cadherin in vitro and during bacterial infection. We found that HtrA targeted mouse and dog E-cadherin equally well, whereas macaque E-cadherin was less fragmented in vitro. We stably re-expressed orthologous E-cadherin (Cdh1) in a CRISPR/Cas9-mediated cdh1 knockout cell line to investigate E-cadherin shedding upon infection using H. pylori wildtype, an isogenic htrA deletion mutant, or complemented mutants as bacterial paradigms. In Western blot analyses and super-resolution microscopy, we demonstrated that H. pylori efficiently cleaved E-cadherin orthologues in an HtrA-dependent manner. These data extend previous knowledge to HtrA-mediated E-cadherin release in mammals, which may shed new light on bacterial infections in non-human organisms. MDPI 2022-02-24 /pmc/articles/PMC8945801/ /pubmed/35327548 http://dx.doi.org/10.3390/biom12030356 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Bernegger, Sabine Hutterer, Evelyn Zarzecka, Urszula Schmidt, Thomas P. Huemer, Markus Widlroither, Isabella Posselt, Gernot Skorko-Glonek, Joanna Wessler, Silja E-Cadherin Orthologues as Substrates for the Serine Protease High Temperature Requirement A (HtrA) |
title | E-Cadherin Orthologues as Substrates for the Serine Protease High Temperature Requirement A (HtrA) |
title_full | E-Cadherin Orthologues as Substrates for the Serine Protease High Temperature Requirement A (HtrA) |
title_fullStr | E-Cadherin Orthologues as Substrates for the Serine Protease High Temperature Requirement A (HtrA) |
title_full_unstemmed | E-Cadherin Orthologues as Substrates for the Serine Protease High Temperature Requirement A (HtrA) |
title_short | E-Cadherin Orthologues as Substrates for the Serine Protease High Temperature Requirement A (HtrA) |
title_sort | e-cadherin orthologues as substrates for the serine protease high temperature requirement a (htra) |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945801/ https://www.ncbi.nlm.nih.gov/pubmed/35327548 http://dx.doi.org/10.3390/biom12030356 |
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