Receptor-mediated transcytosis of botulinum neurotoxin A through intestinal cell monolayers
- 28 September 2007
- journal article
- Published by Hindawi Limited in Cellular Microbiology
- Vol. 10 (2), 375-387
- https://doi.org/10.1111/j.1462-5822.2007.01051.x
Abstract
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.Keywords
This publication has 49 references indexed in Scilit:
- SV2 Is the Protein Receptor for Botulinum Neurotoxin AScience, 2006
- The synaptic vesicle protein 2C mediates the uptake of botulinum neurotoxin A into phrenic nervesFEBS Letters, 2006
- Interaction between the two subdomains of the C‐terminal part of the botulinum neurotoxin A is essential for the generation of protective antibodiesFEBS Letters, 2004
- The receptor and transporter for internalization of Clostridium botulinum type C progenitor toxin into HT-29 cellsBiochemical and Biophysical Research Communications, 2004
- Two Carbohydrate Binding Sites in the HCC-domain of Tetanus Neurotoxin are Required for ToxicityJournal of Molecular Biology, 2003
- Synaptic Vesicle Protein 2, A New Neuroendocrine Cell MarkerThe American Journal of Pathology, 2000
- Clostridium perfringens Iota Toxin: Binding Studies and Characterization of Cell Surface Receptor by Fluorescence-Activated CytometryInfection and Immunity, 2000
- Gangliosides are the binding substances in neural cells for tetanus and botulinum toxins in miceBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1999
- botR/A is a positive regulator of botulinum neurotoxin and associated non‐toxin protein genes in Clostridium botulinum AMolecular Microbiology, 1998
- The high‐affinity binding of Clostridium botulinum type B neurotoxin to synaptotagmin II associated with gangliosides GT1b/GD1aFEBS Letters, 1996