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Submitted on December 9, 2005
Accepted on March 3, 2006
SV2 Is the Protein Receptor for Botulinum Neurotoxin A
Min Dong 1, Felix Yeh 2, William H. Tepp 3, Camin Dean 1, Eric A. Johnson 3, Roger Janz 4, Edwin R. Chapman 2*
1 Howard Hughes Medical Institute and Department of Physiology, University of Wisconsin, Madison, WI 53706, USA. 2 Howard Hughes Medical Institute and Department of Physiology, University of Wisconsin, Madison, WI 53706, USA; 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.
How the widely used botulinum neurotoxin A (BoNT/A) recognizesand enters neurons is poorly understood. Here we found thatBoNT/A enters neurons by binding to the synaptic vesicle proteinSV2 (isoforms A, B and C). Fragments of SV2 that harbor thetoxin interaction domain inhibited BoNT/A binding to neurons.BoNT/A binding to SV2A/B knockout hippocampal neurons was abolishedand was restored by expressing SV2A, B or C. Knock-down of SV2in PC12 and Neuro-2a cells also inhibited entry of BoNT/A, whichcould be restored by expressing SV2 isoforms. Finally, micelacking an SV2 isoform (SV2B) displayed reduced sensitivityto BoNT/A. Thus, SV2 acts as the protein receptor for BoNT/A.
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