Source:http://linkedlifedata.com/resource/pubmed/id/19016790
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2009-1-15
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pubmed:abstractText |
Botulinum neurotoxins (BoNTs) are often acquired from the digestive tract and specifically target neuromuscular junctions where they cause an inhibition of acetylcholine release. A transcytotic mechanism has been evidenced in epithelial intestinal cells, which delivers whole BoNTs across the intestinal barrier, whereas BoNTs enter motoneurons through a pathway that permits the translocation of light chain into the cytosol. We used fluorescent BoNT/A C-terminal part of H chain (Hc) that mediates toxin binding to cell receptors to monitor toxin entry into NG108-15 neuronal cells as well as into Caco-2 and m-IC(cl2) intestinal cells. BoNT/A Hc receptors were found to be distributed in membrane structures closely associated to cholesterol-enriched microdomains, but distinct from detergent-resistant microdomains in both cell types. BoNT/A Hc was trapped into endocytic vesicles, which progressively migrated to a perinuclear area in NG108-15 cells, and in a more scattered manner in intestinal cells. In both cell types, BoNT/A Hc entered through a dynamin- and intersectin-dependent pathway, reached an early endosomal compartment labelled with early endosome antigen 1. In neuronal cells, BoNT/A Hc entered mainly via a clathrin-dependent pathway, in contrast to intestinal cells where it followed a Cdc42-dependent pathway, supporting a differential toxin routing in both cell types.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Vesicular...,
http://linkedlifedata.com/resource/pubmed/chemical/Botulinum Toxins, Type A,
http://linkedlifedata.com/resource/pubmed/chemical/Clathrin,
http://linkedlifedata.com/resource/pubmed/chemical/Dynamins,
http://linkedlifedata.com/resource/pubmed/chemical/cdc42 GTP-Binding Protein,
http://linkedlifedata.com/resource/pubmed/chemical/intersectin 1
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1462-5822
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
289-308
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:19016790-Adaptor Proteins, Vesicular Transport,
pubmed-meshheading:19016790-Botulinum Toxins, Type A,
pubmed-meshheading:19016790-Cell Line,
pubmed-meshheading:19016790-Cell Membrane,
pubmed-meshheading:19016790-Clathrin,
pubmed-meshheading:19016790-Cytoplasm,
pubmed-meshheading:19016790-Dynamins,
pubmed-meshheading:19016790-Epithelial Cells,
pubmed-meshheading:19016790-Humans,
pubmed-meshheading:19016790-Neurons,
pubmed-meshheading:19016790-Protein Transport,
pubmed-meshheading:19016790-Transport Vesicles,
pubmed-meshheading:19016790-cdc42 GTP-Binding Protein
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pubmed:year |
2009
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pubmed:articleTitle |
Differential entry of botulinum neurotoxin A into neuronal and intestinal cells.
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pubmed:affiliation |
Unité des Bactéries anaérobies et Toxines, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris cedex, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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