SV2 Is the Protein Receptor for Botulinum Neurotoxin A
Min Dong,1
Felix Yeh,1,2
William H. Tepp,3
Camin Dean,1
Eric A. Johnson,3
Roger Janz,4
Edwin R. Chapman1,2*
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.
1 Howard Hughes Medical Institute and Department of Physiology, University of Wisconsin, Madison, WI 53706, USA.
2 Molecular and Cellular Pharmacology Program, University of Wisconsin, Madison, WI 53706, USA.
3 Department of Food Microbiology and Toxicology, University of Wisconsin, Madison, WI 53706, USA.
4 W. M. Keck Center for Learning and Memory and Department of Neurobiology and Anatomy, University of Texas–Houston Medical School, Houston, TX 77030, USA.
* To whom correspondence should be addressed: E-mail: chapman{at}physiology.wisc.edu
