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

• Amatsu Sho

• Matsumura Takuhiro

• Yutani Masahiro

• Fujinaga Yukako

• 阿松 翔

• 松村 拓大

• 油谷 雅広

• 藤永 由佳子

抄録

金沢大学医薬保健研究域医学系

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. © 2017 The Societies and John Wiley & Sons Australia, Ltd

Embargo Period 12 months

収録刊行物

• Microbiology and Immunology

  Microbiology and Immunology 62 (2), 80-89, 2018-02-01

  日本細菌学会 Japanese Society for Bacteriology / Wiley

キーワード

• botulinum neurotoxin
• epithelial barrier
• hemagglutinin
• multivalent binding

詳細情報

• CRID: 1390572174913916416
• NII論文ID: 120006457636
• NII書誌ID: AA00738350
• ISSN: 03855600
• ISSN: 13480421
• DOI: 10.24517/00050508
• DOI: 10.1111/1348-0421.12565
• NDL書誌ID: 028853951
• Web Site: http://hdl.handle.net/2297/00050508
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I028853951
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2F1348-0421.12565
• Web Site: https://onlinelibrary.wiley.com/doi/pdf/10.1111/1348-0421.12565
• Web Site: https://search.jamas.or.jp/link/ui/2019023861
• 本文言語コード: en
• データソース種別:
  • JaLC
  • IRDB
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN