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MIRAVA POLYSCOPE – All in one and on for all: the perfect image
Science beyond Barriers

abberior instruments

Microbiology

2022
Biomolecules

E-Cadherin Orthologues as Substrates for the Serine Protease High Temperature Requirement A (HtrA)

Authors:

Bernegger, S., Hutterer, E., Zarzecka, U., Schmidt, T. P., Huemer, M., Widlroither, I., ... & Wessler, S.

Keywords:

HtrA, E-cadherin, infection, pathogens

Abstract:

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.

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Superresolution & Confocal Systems

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Superresolution & Confocal Modules

  • Overview
  • MINFLUX Module
  • MATRIX Detector
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  • FLEXPOSURE Illumination
  • RAYSHAPE Mirror
  • TRUESHARP Deconvolution
  • EASY3D
  • RAINBOW Detection
  • STED Lasers
  • Autoalignment
  • Autofocus
  • Excitation Lasers
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  • abberior STAR
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