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Crosslinking of a Peritrophic Matrix Protein Protects Gut Epithelia from Bacterial Exotoxins
Transglutaminase (TG) catalyzes protein-protein crosslinking, which has important and diverse roles in vertebrates and invertebrates. Here we demonstrate that Drosophila TG crosslinks drosocrystallin, a peritrophic matrix protein, to form a stable fiber structure on the gut peritrophic matrix. RNA i...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646701/ https://www.ncbi.nlm.nih.gov/pubmed/26506243 http://dx.doi.org/10.1371/journal.ppat.1005244 |
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author | Shibata, Toshio Maki, Kouki Hadano, Jinki Fujikawa, Takumi Kitazaki, Kazuki Koshiba, Takumi Kawabata, Shun-ichiro |
author_facet | Shibata, Toshio Maki, Kouki Hadano, Jinki Fujikawa, Takumi Kitazaki, Kazuki Koshiba, Takumi Kawabata, Shun-ichiro |
author_sort | Shibata, Toshio |
collection | PubMed |
description | Transglutaminase (TG) catalyzes protein-protein crosslinking, which has important and diverse roles in vertebrates and invertebrates. Here we demonstrate that Drosophila TG crosslinks drosocrystallin, a peritrophic matrix protein, to form a stable fiber structure on the gut peritrophic matrix. RNA interference (RNAi) of the TG gene was highly lethal in flies and induced apoptosis of gut epithelial cells after oral infection with Pseudomonas entomophila. Moreover, AprA, a metalloprotease secreted by P. entomophila, digested non-crosslinked drosocrystallin fibers, but not drosocrystallin fibers crosslinked by TG. In vitro experiments using recombinant drosocrystallin and monalysin proteins demonstrated that monalysin, a pore-forming exotoxin of P. entomophila, was adsorbed on the crosslinked drosocrystallin fibers in the presence of P. entomophila culture supernatant. In addition, gut-specific TG-RNAi flies had a shorter lifespan than control flies after ingesting P. entomophila, whereas the lifespan after ingesting AprA-knockout P. entomophila was at control levels. We conclude that drosocrystallin fibers crosslinked by TG, but not non-crosslinked drosocrystallin fibers, form an important physical barrier against exotoxins of invading pathogenic microbes. |
format | Online Article Text |
id | pubmed-4646701 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-46467012015-12-02 Crosslinking of a Peritrophic Matrix Protein Protects Gut Epithelia from Bacterial Exotoxins Shibata, Toshio Maki, Kouki Hadano, Jinki Fujikawa, Takumi Kitazaki, Kazuki Koshiba, Takumi Kawabata, Shun-ichiro PLoS Pathog Research Article Transglutaminase (TG) catalyzes protein-protein crosslinking, which has important and diverse roles in vertebrates and invertebrates. Here we demonstrate that Drosophila TG crosslinks drosocrystallin, a peritrophic matrix protein, to form a stable fiber structure on the gut peritrophic matrix. RNA interference (RNAi) of the TG gene was highly lethal in flies and induced apoptosis of gut epithelial cells after oral infection with Pseudomonas entomophila. Moreover, AprA, a metalloprotease secreted by P. entomophila, digested non-crosslinked drosocrystallin fibers, but not drosocrystallin fibers crosslinked by TG. In vitro experiments using recombinant drosocrystallin and monalysin proteins demonstrated that monalysin, a pore-forming exotoxin of P. entomophila, was adsorbed on the crosslinked drosocrystallin fibers in the presence of P. entomophila culture supernatant. In addition, gut-specific TG-RNAi flies had a shorter lifespan than control flies after ingesting P. entomophila, whereas the lifespan after ingesting AprA-knockout P. entomophila was at control levels. We conclude that drosocrystallin fibers crosslinked by TG, but not non-crosslinked drosocrystallin fibers, form an important physical barrier against exotoxins of invading pathogenic microbes. Public Library of Science 2015-10-27 /pmc/articles/PMC4646701/ /pubmed/26506243 http://dx.doi.org/10.1371/journal.ppat.1005244 Text en © 2015 Shibata et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Shibata, Toshio Maki, Kouki Hadano, Jinki Fujikawa, Takumi Kitazaki, Kazuki Koshiba, Takumi Kawabata, Shun-ichiro Crosslinking of a Peritrophic Matrix Protein Protects Gut Epithelia from Bacterial Exotoxins |
title | Crosslinking of a Peritrophic Matrix Protein Protects Gut Epithelia from Bacterial Exotoxins |
title_full | Crosslinking of a Peritrophic Matrix Protein Protects Gut Epithelia from Bacterial Exotoxins |
title_fullStr | Crosslinking of a Peritrophic Matrix Protein Protects Gut Epithelia from Bacterial Exotoxins |
title_full_unstemmed | Crosslinking of a Peritrophic Matrix Protein Protects Gut Epithelia from Bacterial Exotoxins |
title_short | Crosslinking of a Peritrophic Matrix Protein Protects Gut Epithelia from Bacterial Exotoxins |
title_sort | crosslinking of a peritrophic matrix protein protects gut epithelia from bacterial exotoxins |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4646701/ https://www.ncbi.nlm.nih.gov/pubmed/26506243 http://dx.doi.org/10.1371/journal.ppat.1005244 |
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