論文

査読有り 国際誌
2018年2月1日

Multivalency effects of hemagglutinin component of type B botulinum neurotoxin complex on epithelial barrier disruption

Microbiology and Immunology
  • Sho Amatsu
  • ,
  • Takuhiro Matsumura
  • ,
  • Masahiro Yutani
  • ,
  • Yukako Fujinaga

62
2
開始ページ
80
終了ページ
89
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/1348-0421.12565
出版者・発行元
Blackwell Publishing Asia

Hemagglutinin (HA) is one of the components of botulinum neurotoxin (BoNT) complexes and it promotes the absorption of BoNT through the intestinal epithelium by at least two specific mechanisms: cell surface attachment by carbohydrate binding, and epithelial barrier disruption by E-cadherin binding. It is known that HA forms a three-arm structure, in which each of three protomers has three carbohydrate-binding sites and one E-cadherin-binding site. A three-arm form of HA is considered to bind to these ligands simultaneously. In the present study, we investigated how the multivalency effect of HA influences its barrier-disrupting activity. We prepared type B full-length HA (three-arm form) and mini-HA, which is a deletion mutant lacking the trimer-forming domain. Size-exclusion chromatography analysis showed that mini-HA exists as dimers (two-arm form) and monomers (one-arm form), which are then separated. We examined the multivalency effect of HA on the barrier-disrupting activity, the E-cadherin-binding activity, and the attachment activity to the basolateral cell surface. Our results showed that HA initially attaches to the basal surface of Caco-2 cells by carbohydrate binding and then moves to the lateral cell surface, where the HA acts to disrupt the epithelial barrier. Our results showed that the multivalency effect of HA enhances the barrier-disrupting activity in Caco-2 cells. We found that basal cell surface attachment and binding ability to immobilized E-cadherin were enhanced by the multivalency effect of HA. These results suggest that at least these two factors induced by the multivalency effect of HA cause the enhancement of the barrier-disrupting activity.


リンク情報
DOI
https://doi.org/10.1111/1348-0421.12565
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29266585
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000425182600002&DestApp=WOS_CPL
ID情報
  • DOI : 10.1111/1348-0421.12565
  • ISSN : 1348-0421
  • ISSN : 0385-5600
  • PubMed ID : 29266585
  • SCOPUS ID : 85042155593
  • Web of Science ID : WOS:000425182600002

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