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Disruption of lipid rafts enhances activity of botulinum neurotoxin serotype A
- Source :
- Toxicon. 48:1035-1045
- Publication Year :
- 2006
- Publisher :
- Elsevier BV, 2006.
-
Abstract
- Botulinum neurotoxin serotype A (BoNT/A), one of seven serotypes of botulinum neurotoxin, is taken up by neurons of the peripheral nervous system. Within the neurons it catalyzes cleavage of the synaptosomal-associated protein having a mass of 25kDa, SNAP-25, thereby blocking neurotransmission. BoNT/A has been shown to interact with SV2, as well as gangliosides that are often found in lipid rafts. Lipid rafts are microdomains that can be found on the outer leaflet of the plasma membrane and are enriched in cholesterol and glycosphingolipids. To determine whether lipid rafts are needed for BoNT/A activity, those associated with the plasma membranes of murine N2a neuroblastoma cells were disrupted using either methyl-beta-cyclodextrin or filipin. Disruption of cholesterol-containing lipid rafts by either reagent did not prevent the action of BoNT/A on N2a cells, in fact activity was enhanced. While our results indicate that disruption of lipid rafts enhances BoNT/A activity, disruption of clathrin-dependent endocytosis appeared to be inhibitory.
- Subjects :
- Cholera Toxin
Synaptosomal-Associated Protein 25
Neurotoxins
G(M1) Ganglioside
Neurotransmission
Toxicology
Endocytosis
Filipin
Clathrin
Mice
chemistry.chemical_compound
Membrane Microdomains
Cell Line, Tumor
Animals
Botulinum Toxins, Type A
Lipid raft
Ganglioside
biology
Cholesterol
beta-Cyclodextrins
Clathrin-Coated Vesicles
Cell biology
chemistry
Biochemistry
Cell culture
biology.protein
lipids (amino acids, peptides, and proteins)
Subjects
Details
- ISSN :
- 00410101
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Toxicon
- Accession number :
- edsair.doi.dedup.....122ca567242692ab69087d668b410d7f