Document Detail


Receptor-mediated transcytosis of botulinum neurotoxin A through intestinal cell monolayers.
MedLine Citation:
PMID:  17900298     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Botulism is mainly acquired by the oral route, and botulinum neurotoxin (BoNT) escapes the gastrointestinal tract by crossing the digestive epithelial barrier prior to gaining access to the nerve endings. Here, we show that biologically active BoNT/A crosses intestinal cell monolayers via a receptor-mediated transcytosis, including a transport inhibition at 4 degrees C and a passage at 37 degrees C in a saturable manner within 30-60 min. BoNT/A passage rate was about 10-fold more efficient through the intestinal crypt cell line m-IC(cl2), than through the carcinoma Caco-2 or T84 cells, and was not increased when BoNT/A was associated with the non-toxic proteins (botulinum complex). Like for neuronal cells, BoNT/A binding to intestinal cells was mediated by the half C-terminal domain as tested by fluorescence-activated cytometry and by transcytosis competition assay. A 'double receptor model' has been proposed in which BoNT/A interacts with gangliosides of GD(1b) and GT(1b) series as well as SV2 protein. Gangliosides of GD(1b) and GT(1b) series and recombinant intravesicular SV2-C domain partially impaired BoNT/A transcytosis, suggesting a putative role of gangliosides and SV2 or a related protein in BoNT/A transcytosis through Caco-2 and m-IC(cl2) cells.
Authors:
Aurélie Couesnon; Yannick Pereira; Michel R Popoff
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-09-28
Journal Detail:
Title:  Cellular microbiology     Volume:  10     ISSN:  1462-5822     ISO Abbreviation:  Cell. Microbiol.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-01-14     Completed Date:  2008-03-07     Revised Date:  2008-08-14    
Medline Journal Info:
Nlm Unique ID:  100883691     Medline TA:  Cell Microbiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  375-87     Citation Subset:  IM    
Affiliation:
Unité des bactéries anaérobies et Toxines, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris cedex, France.
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MeSH Terms
Descriptor/Qualifier:
Binding Sites
Biological Transport / physiology
Botulinum Toxin Type A / chemistry,  metabolism*
Caco-2 Cells
Cell Line
Cell Separation
Endocytosis / physiology
Epithelial Cells / metabolism
Flow Cytometry
Gangliosides / chemistry,  metabolism
Humans
Intestinal Mucosa / cytology,  metabolism*
Membrane Glycoproteins / chemistry,  metabolism
Protein Isoforms / chemistry,  metabolism
Protein Structure, Tertiary
Receptors, Cell Surface / chemistry,  metabolism*
Chemical
Reg. No./Substance:
0/Botulinum Toxin Type A; 0/Gangliosides; 0/Membrane Glycoproteins; 0/Protein Isoforms; 0/Receptors, Cell Surface; 19553-76-5/ganglioside, GD1b; 59247-13-1/trisialoganglioside GT1

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