SV2 Is the Protein Receptor for Botulinum Neurotoxin A
Howard Hughes Medical Institute · University of Wisconsin–Madison · +1 more institution
Abstract
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.
Citation impact
- FWCI
- 40.70
- Percentile
- 100%
- References
- 31
Authors
7- MDMin Dong
Howard Hughes Medical Institute, University of Wisconsin–Madison, The University of Texas Health Science Center at Houston
- FLFelix L. Yeh
Howard Hughes Medical Institute, University of Wisconsin–Madison, The University of Texas Health Science Center at Houston
- WHWilliam H. Tepp
Howard Hughes Medical Institute, University of Wisconsin–Madison, The University of Texas Health Science Center at Houston
- CDCamin Dean
Howard Hughes Medical Institute, University of Wisconsin–Madison, The University of Texas Health Science Center at Houston
- EAEric A. Johnson
Howard Hughes Medical Institute, University of Wisconsin–Madison, The University of Texas Health Science Center at Houston
Topics & keywords
- Gene isoform
- Synaptic vesicle
- Botulinum neurotoxin
- Neurotoxin
- Receptor
- Chemistry
- Hippocampal formation
- Pharmacology