Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells

Abstract Background High temperature requirement A (HtrA) is an active serine protease secreted by the group-I carcinogen Helicobacter pylori (H. pylori). The human cell adhesion protein and tumor suppressor E-cadherin (hCdh1) expressed on the surface of gastric epithelial cells was identified as th...

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Autores principales:	Sabine Bernegger, Robert Vidmar, Marko Fonovic, Gernot Posselt, Boris Turk, Silja Wessler
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Desmoglein-2 E-cadherin Helicobacter pylori HtrA Protease Medicine R Cytology QH573-671
Acceso en línea:	https://doaj.org/article/16a0e2b933244d749b94d26a156c2a11
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spelling	oai:doaj.org-article:16a0e2b933244d749b94d26a156c2a112021-11-08T10:44:47ZIdentification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells10.1186/s12964-021-00788-x1478-811Xhttps://doaj.org/article/16a0e2b933244d749b94d26a156c2a112021-11-01T00:00:00Zhttps://doi.org/10.1186/s12964-021-00788-xhttps://doaj.org/toc/1478-811XAbstract Background High temperature requirement A (HtrA) is an active serine protease secreted by the group-I carcinogen Helicobacter pylori (H. pylori). The human cell adhesion protein and tumor suppressor E-cadherin (hCdh1) expressed on the surface of gastric epithelial cells was identified as the first HtrA substrate. HtrA-mediated hCdh1 cleavage and subsequent disruption of intercellular adhesions are considered as important steps in H. pylori pathogenesis. In this study, we performed a proteomic profiling of H. pylori HtrA (HpHtrA) to decipher the complex mechanism of H. pylori interference with the epithelial barrier integrity. Results Using a proteomic approach we identified human desmoglein-2 (hDsg2), neuropilin-1, ephrin-B2, and semaphorin-4D as novel extracellular HpHtrA substrates and confirmed the well characterized target hCdh1. HpHtrA-mediated hDsg2 cleavage was further analyzed by in vitro cleavage assays using recombinant proteins. In infection experiments, we demonstrated hDsg2 shedding from H. pylori-colonized MKN28 and NCI-N87 cells independently of pathogen-induced matrix-metalloproteases or ADAM10 and ADAM17. Conclusions Characterizing the substrate specificity of HpHtrA revealed efficient hDsg2 cleavage underlining the importance of HpHtrA in opening intercellular junctions. Video AbstractSabine BerneggerRobert VidmarMarko FonovicGernot PosseltBoris TurkSilja WesslerBMCarticleDesmoglein-2E-cadherinHelicobacter pyloriHtrAProteaseMedicineRCytologyQH573-671ENCell Communication and Signaling, Vol 19, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Desmoglein-2 E-cadherin Helicobacter pylori HtrA Protease Medicine R Cytology QH573-671
spellingShingle	Desmoglein-2 E-cadherin Helicobacter pylori HtrA Protease Medicine R Cytology QH573-671 Sabine Bernegger Robert Vidmar Marko Fonovic Gernot Posselt Boris Turk Silja Wessler Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells
description	Abstract Background High temperature requirement A (HtrA) is an active serine protease secreted by the group-I carcinogen Helicobacter pylori (H. pylori). The human cell adhesion protein and tumor suppressor E-cadherin (hCdh1) expressed on the surface of gastric epithelial cells was identified as the first HtrA substrate. HtrA-mediated hCdh1 cleavage and subsequent disruption of intercellular adhesions are considered as important steps in H. pylori pathogenesis. In this study, we performed a proteomic profiling of H. pylori HtrA (HpHtrA) to decipher the complex mechanism of H. pylori interference with the epithelial barrier integrity. Results Using a proteomic approach we identified human desmoglein-2 (hDsg2), neuropilin-1, ephrin-B2, and semaphorin-4D as novel extracellular HpHtrA substrates and confirmed the well characterized target hCdh1. HpHtrA-mediated hDsg2 cleavage was further analyzed by in vitro cleavage assays using recombinant proteins. In infection experiments, we demonstrated hDsg2 shedding from H. pylori-colonized MKN28 and NCI-N87 cells independently of pathogen-induced matrix-metalloproteases or ADAM10 and ADAM17. Conclusions Characterizing the substrate specificity of HpHtrA revealed efficient hDsg2 cleavage underlining the importance of HpHtrA in opening intercellular junctions. Video Abstract
format	article
author	Sabine Bernegger Robert Vidmar Marko Fonovic Gernot Posselt Boris Turk Silja Wessler
author_facet	Sabine Bernegger Robert Vidmar Marko Fonovic Gernot Posselt Boris Turk Silja Wessler
author_sort	Sabine Bernegger
title	Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells
title_short	Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells
title_full	Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells
title_fullStr	Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells
title_full_unstemmed	Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells
title_sort	identification of desmoglein-2 as a novel target of helicobacter pylori htra in epithelial cells
publisher	BMC
publishDate	2021
url	https://doaj.org/article/16a0e2b933244d749b94d26a156c2a11
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Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells

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