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Identification of Desmoglein-2 as a novel target of Helicobacter pylori HtrA in epithelial cells.
- Source :
-
Cell Communication & Signaling . 11/6/2021, Vol. 19 Issue 1, p1-12. 12p. - Publication Year :
- 2021
-
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. 6h_G33ukTTgCSbc2oAPked Video Abstract [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1478811X
- Volume :
- 19
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Cell Communication & Signaling
- Publication Type :
- Academic Journal
- Accession number :
- 153435697
- Full Text :
- https://doi.org/10.1186/s12964-021-00788-x