
pmid: 16543415
How the widely used botulinum neurotoxin A (BoNT/A) recognizes and enters neurons is poorly understood. We found that BoNT/A enters neurons by binding to the synaptic vesicle protein SV2 (isoforms A, B, and C). Fragments of SV2 that harbor the toxin interaction domain inhibited BoNT/A from binding to neurons. BoNT/A binding to SV2A and SV2B knockout hippocampal neurons was abolished and was restored by expressing SV2A, SV2B, or SV2C. Reduction of SV2 expression in PC12 and Neuro-2a cells also inhibited entry of BoNT/A, which could be restored by expressing SV2 isoforms. Finally, mice that lacked an SV2 isoform (SV2B) displayed reduced sensitivity to BoNT/A. Thus, SV2 acts as the protein receptor for BoNT/A.
Mice, Knockout, Neurons, Membrane Glycoproteins, Neuromuscular Junction, Nerve Tissue Proteins, Hippocampus, PC12 Cells, Endocytosis, Cell Line, Protein Structure, Tertiary, Rats, R-SNARE Proteins, Mice, Synaptotagmins, Animals, Protein Isoforms, Synaptic Vesicles, Botulinum Toxins, Type A, Cells, Cultured, Protein Binding
Mice, Knockout, Neurons, Membrane Glycoproteins, Neuromuscular Junction, Nerve Tissue Proteins, Hippocampus, PC12 Cells, Endocytosis, Cell Line, Protein Structure, Tertiary, Rats, R-SNARE Proteins, Mice, Synaptotagmins, Animals, Protein Isoforms, Synaptic Vesicles, Botulinum Toxins, Type A, Cells, Cultured, Protein Binding
| citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | 707 | |
| popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network. | Top 1% | |
| influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Top 1% | |
| impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 0.1% |
