論文

査読有り 国際誌
2015年9月

Clostridium botulinum type C hemagglutinin affects the morphology and viability of cultured mammalian cells via binding to the ganglioside GM3

FEBS JOURNAL
  • Yo Sugawara
  • ,
  • Masao Iwamori
  • ,
  • Takuhiro Matsumura
  • ,
  • Masahiro Yutani
  • ,
  • Sho Amatsu
  • ,
  • Yukako Fujinaga

282
17
開始ページ
3334
終了ページ
3347
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1111/febs.13346
出版者・発行元
WILEY-BLACKWELL

Botulinum neurotoxin is conventionally divided into seven serotypes, designated A-G, and is produced as large protein complexes through associations with non-toxic components, such as hemagglutinin (HA) and non-toxic non-HA. These non-toxic proteins dramatically enhance the oral toxicity of the toxin complex. HA is considered to have a role in toxin transport through the intestinal epithelium by carbohydrate binding and epithelial barrier-disrupting activity. Type A and B HAs disrupt E-cadher-in-mediated cell adhesion, and, in turn, the intercellular epithelial barrier. Type C HA (HA/C) disrupts the barrier function by affecting cell morphology and viability, the mechanism of which remains unknown. In this study, we identified GM3 as the target molecule of HA/C. We found that sialic acid binding of HA is essential for the activity. It was abolished when cells were pre-treated with an inhibitor of ganglioside synthesis. Consistent with this, HA/C bound to a-series gangliosides in a glycan array. In parallel, we isolated clones resistant to HA/C activity from a susceptible mouse fibroblast strain. These cells lacked expression of ST-I, the enzyme that transfers sialic acid to lactosylceramide to yield GM3. These clones became sensitive to HA/C activity when GM3 was expressed by transfection with the ST-I gene. The sensitivity of fibroblasts to HA/C was reduced by expressing ganglioside synthesis genes whose products utilize GM3 as a substrate and consequently generate other a-series gangliosides, suggesting a GM3-specific mechanism. Our results demonstrate that HA/C affects cells in a GM3-dependent manner.


リンク情報
DOI
https://doi.org/10.1111/febs.13346
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26077172
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000360629200008&DestApp=WOS_CPL
ID情報
  • DOI : 10.1111/febs.13346
  • ISSN : 1742-464X
  • eISSN : 1742-4658
  • PubMed ID : 26077172
  • Web of Science ID : WOS:000360629200008

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