SV2 is the protein receptor for botulinum neurotoxin A

Science. 2006 Apr 28;312(5773):592-6. doi: 10.1126/science.1123654. Epub 2006 Mar 16.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Botulinum Toxins, Type A / metabolism*
  • Botulinum Toxins, Type A / toxicity
  • Cell Line
  • Cells, Cultured
  • Endocytosis
  • Hippocampus / cytology
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuromuscular Junction / metabolism
  • Neurons / metabolism*
  • PC12 Cells
  • Protein Binding
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • R-SNARE Proteins / metabolism
  • Rats
  • Synaptic Vesicles / metabolism*
  • Synaptotagmins / metabolism


  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Protein Isoforms
  • R-SNARE Proteins
  • Sv2a protein, mouse
  • Sv2a protein, rat
  • Synaptotagmins
  • Botulinum Toxins, Type A