title: Botulinum hemagglutinin disrupts the intercellular epithelial barrier by directly binding E-cadherin.
abstract: 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.
authors.affiliation: Laboratory for Infection Cell Biology, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Sugawara
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Matsumura
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takegahara
authors.forename: Yingji
authors.initials: Y
authors.lastname: Jin
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Tsukasaki
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takeichi
authors.forename: Yukako
authors.initials: Y
authors.lastname: Fujinaga
mesh_terms: D000818:Animals; D001905:Botulinum Toxins / Q000378:metabolism* / Q000494:pharmacology; D015820:Cadherins / Q000737:chemistry / Q000378:metabolism; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006388:Hemagglutinins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D051381:Rats
chemical_list: D015820:Cadherins; D006388:Hemagglutinins; D001905:Botulinum Toxins
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