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...

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Bibliographic Details
Published in:The Journal of cell biology 2010-05, Vol.189 (4), p.691-700
Main Authors: Sugawara, Yo, Matsumura, Takuhiro, Takegahara, Yuki, Jin, Yingji, Tsukasaki, Yoshikazu, Takeichi, Masatoshi, Fujinaga, Yukako
Format: Article
Language:English
Subjects:
Animals
Antibodies
Botulinum Toxins - metabolism
Botulinum Toxins - pharmacology
Botulism
Caco 2 cells
Cadherins
Cadherins - chemistry
Cadherins - metabolism
Canines
Cattle
Cell adhesion
Cell adhesion & migration
Cell Adhesion - drug effects
Cell Line
Cellular biology
Delta cells
Dogs
Epithelial cells
Epithelial Cells - cytology
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Gram-positive bacteria
Hemagglutinins - metabolism
Hemagglutinins - pharmacology
Humans
Intercellular junctions
L cells
Mice
Neurotoxicity
Proteins
Rats
Toxins
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Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200910119