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Science. 2006 Apr 28;312(5773):592-6. Epub 2006 Mar 16.

SV2 is the protein receptor for botulinum neurotoxin A.

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  • 1Howard Hughes Medical Institute and Department of Physiology, University of Wisconsin, Madison, WI 53706, USA.

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.

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PMID:
16543415
[PubMed - indexed for MEDLINE]
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