| RRC ID |
18735
|
| Author |
Sugawara Y, Matsumura T, Takegahara Y, Jin Y, Tsukasaki Y, Takeichi M, Fujinaga Y.
|
| Title |
Botulinum hemagglutinin disrupts the intercellular epithelial barrier by directly binding E-cadherin.
|
| Journal |
J Cell Biol
|
| 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.
|
| Volume |
189(4)
|
| Pages |
691-700
|
| Published |
2010-5-17
|
| DOI |
10.1083/jcb.200910119
|
| PII |
jcb.200910119
|
| PMID |
20457762
|
| PMC |
PMC2872904
|
| MeSH |
Animals
Botulinum Toxins / metabolism*
Botulinum Toxins / pharmacology
Cadherins / chemistry
Cadherins / metabolism
Cattle
Cell Adhesion / drug effects
Cell Line
Dogs
Epithelial Cells / cytology*
Epithelial Cells / drug effects
Epithelial Cells / metabolism
Hemagglutinins / metabolism*
Hemagglutinins / pharmacology
Humans
Mice
Rats
|
| IF |
8.811
|
| Times Cited |
67
|
|
WOS Category
|
CELL BIOLOGY
|
| Resource |
| Human and Animal Cells |
MDBK(RCB0180)
NBT-T1(RCB1369) |
