Pasteurella multocida Toxin as a Transporter of Non-Cell-Permeating Proteins
| Autor: | Joachim H. C. Orth, Doris Jehle, Carsten Schwan, Stefan Bergmann, Klaus Aktories |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Cell Membrane Permeability
Cell Survival G protein Recombinant Fusion Proteins Bacterial Toxins Immunology Golgi Apparatus Endosomes Biology medicine.disease_cause Microbiology Cytosol Bacterial Proteins Cell surface receptor Heterotrimeric G protein medicine Humans Diphtheria Toxin Cloning Molecular Diphtheria toxin Cellular Microbiology: Pathogen-Host Cell Molecular Interactions Toxin Fusion protein Molecular biology Peptide Fragments Protein Structure Tertiary Transport protein Elongation factor Protein Transport HEK293 Cells Infectious Diseases Parasitology Macrolides Caco-2 Cells Biomarkers Protein Binding |
| Zdroj: | Infection and Immunity. 81:2459-2467 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00429-13 |
| Popis: | The protein toxin Pasteurella multocida toxin (PMT) is the causative agent of atrophic rhinitis in pigs, leading to atrophy of the nasal turbinate bones by affecting osteoblasts and osteoclasts. The mechanism of PMT-induced intoxication is a deamidation of α-subunits of heterotrimeric G proteins, including Gα q , Gα 13 , and Gα i , thereby causing persistent activation of the G proteins. Here we utilized PMT as a transporter of the non-cell-permeating A domain of diphtheria toxin (DTa). Fusion proteins of PMT and DTa ADP-ribosylated elongation factor 2, the natural target of diphtheria toxin, leading to cell toxicity. PMT-DTa effects were competed by PMT, indicating binding to the same cell surface receptor. Fluorescently labeled PMT-DTa and PMT colocalized with specific markers of early and late endosomes. Bafilomycin A, which inhibits vacuolar H + -ATPase, blocked PMT-DTa-induced intoxication of HEK-293 cells. By constructing various PMT-DTa chimeras, we identified a minimal region of PMT necessary for uptake of DTa. The data suggest that PMT is able to transport cargo proteins into eukaryotic cells by utilizing the PMT-specific uptake route. |
| Databáze: | OpenAIRE |
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