SV2 Is the Protein Receptor for Botulinum Neurotoxin A
pmid: 16543415
SV2 Is the Protein Receptor for Botulinum Neurotoxin A
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.
- University of Wisconsin System United States
- University of Wisconsin–Oshkosh United States
- University of Wisconsin–Madison United States
- The University of Texas System United States
- The University of Texas Health Science Center at Houston United States
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
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