The synaptic vesicle protein 2C mediates the uptake of botulinum neurotoxin A into phrenic nerves

FEBS Lett. 2006 Apr 3;580(8):2011-4. doi: 10.1016/j.febslet.2006.02.074. Epub 2006 Mar 7.


Botulinum neurotoxins (BoNTs) inhibit neurotransmitter release by selectively cleaving core components of the vesicular fusion machinery. The synaptic vesicle proteins Synaptotagmin-I and -II act as receptors for BoNT/B and BoNT/G. Here we show that BoNT/A also interacts with a synaptic vesicle protein, the synaptic vesicle glycoprotein 2C (SV2C), but not with the homologous proteins SV2A and SV2B. Binding of BoNT/A occurs at the membrane juxtaposed region preceding transmembrane domain 8. A peptide comprising the intravesicular domain between transmembrane domains 7 and 8 specifically reduces the neurotoxicity of BoNT/A at phrenic nerve preparations demonstrating the physiological relevance of this interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Botulinum Toxins, Type A / antagonists & inhibitors
  • Botulinum Toxins, Type A / metabolism*
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Nerve Tissue Proteins / metabolism*
  • Phrenic Nerve / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Transport
  • Recombinant Fusion Proteins / metabolism


  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Recombinant Fusion Proteins
  • Sv2c protein, mouse
  • Botulinum Toxins, Type A