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Botulinum hemagglutinin disrupts the intercellular epithelial barrier by directly binding E-cadherin
Botulinum neurotoxin is produced by Clostridium botulinum and forms large protein complexes through associations with nontoxic components. We recently found that hemagglutinin (HA), one of the nontoxic components, disrupts the intercellular epithelial barrier; however, the mechanism underlying this...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872904/ https://www.ncbi.nlm.nih.gov/pubmed/20457762 http://dx.doi.org/10.1083/jcb.200910119 |
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author | Sugawara, Yo Matsumura, Takuhiro Takegahara, Yuki Jin, Yingji Tsukasaki, Yoshikazu Takeichi, Masatoshi Fujinaga, Yukako |
author_facet | Sugawara, Yo Matsumura, Takuhiro Takegahara, Yuki Jin, Yingji Tsukasaki, Yoshikazu Takeichi, Masatoshi Fujinaga, Yukako |
author_sort | Sugawara, Yo |
collection | PubMed |
description | Botulinum neurotoxin is produced by Clostridium botulinum and forms large protein complexes through associations with nontoxic components. We recently found that hemagglutinin (HA), one of the nontoxic components, disrupts the intercellular epithelial barrier; however, the mechanism underlying this phenomenon is not known. In this study, we identified epithelial cadherin (E-cadherin) as a target molecule for HA. HA directly binds E-cadherin and disrupts E-cadherin–mediated cell to cell adhesion. Although HA binds human, bovine, and mouse E-cadherin, it does not bind rat or chicken E-cadherin homologues. HA does not interact with other members of the classical cadherin family such as neural and vascular endothelial cadherin. Expression of rat E-cadherin but not mouse rescues Madin–Darby canine kidney cells from HA-induced tight junction (TJ) disruptions. These data demonstrate that botulinum HA directly binds E-cadherin and disrupts E-cadherin–mediated cell to cell adhesion in a species-specific manner and that the HA–E-cadherin interaction is essential for the disruption of TJ function. |
format | Text |
id | pubmed-2872904 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28729042010-11-17 Botulinum hemagglutinin disrupts the intercellular epithelial barrier by directly binding E-cadherin Sugawara, Yo Matsumura, Takuhiro Takegahara, Yuki Jin, Yingji Tsukasaki, Yoshikazu Takeichi, Masatoshi Fujinaga, Yukako J Cell Biol Research Articles Botulinum neurotoxin is produced by Clostridium botulinum and forms large protein complexes through associations with nontoxic components. We recently found that hemagglutinin (HA), one of the nontoxic components, disrupts the intercellular epithelial barrier; however, the mechanism underlying this phenomenon is not known. In this study, we identified epithelial cadherin (E-cadherin) as a target molecule for HA. HA directly binds E-cadherin and disrupts E-cadherin–mediated cell to cell adhesion. Although HA binds human, bovine, and mouse E-cadherin, it does not bind rat or chicken E-cadherin homologues. HA does not interact with other members of the classical cadherin family such as neural and vascular endothelial cadherin. Expression of rat E-cadherin but not mouse rescues Madin–Darby canine kidney cells from HA-induced tight junction (TJ) disruptions. These data demonstrate that botulinum HA directly binds E-cadherin and disrupts E-cadherin–mediated cell to cell adhesion in a species-specific manner and that the HA–E-cadherin interaction is essential for the disruption of TJ function. The Rockefeller University Press 2010-05-17 /pmc/articles/PMC2872904/ /pubmed/20457762 http://dx.doi.org/10.1083/jcb.200910119 Text en © 2010 Sugawara et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Sugawara, Yo Matsumura, Takuhiro Takegahara, Yuki Jin, Yingji Tsukasaki, Yoshikazu Takeichi, Masatoshi Fujinaga, Yukako Botulinum hemagglutinin disrupts the intercellular epithelial barrier by directly binding E-cadherin |
title | Botulinum hemagglutinin disrupts the intercellular epithelial barrier by directly binding E-cadherin |
title_full | Botulinum hemagglutinin disrupts the intercellular epithelial barrier by directly binding E-cadherin |
title_fullStr | Botulinum hemagglutinin disrupts the intercellular epithelial barrier by directly binding E-cadherin |
title_full_unstemmed | Botulinum hemagglutinin disrupts the intercellular epithelial barrier by directly binding E-cadherin |
title_short | Botulinum hemagglutinin disrupts the intercellular epithelial barrier by directly binding E-cadherin |
title_sort | botulinum hemagglutinin disrupts the intercellular epithelial barrier by directly binding e-cadherin |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872904/ https://www.ncbi.nlm.nih.gov/pubmed/20457762 http://dx.doi.org/10.1083/jcb.200910119 |
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