SV2 Is the Protein Receptor for Botulinum Neurotoxin A
Top Cited Papers
- 28 April 2006
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 312 (5773) , 592-596
- https://doi.org/10.1126/science.1123654
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.Keywords
This publication has 30 references indexed in Scilit:
- Synaptic Vesicle Protein 2 Enhances Release Probability at Quiescent SynapsesJournal of Neuroscience, 2006
- Botulinum Neurotoxin A Changes Conformation upon Binding to Ganglioside GT1bBiochemistry, 2004
- Botulinum Neurotoxin A Activity Is Dependent upon the Presence of Specific Gangliosides in Neuroblastoma Cells Expressing Synaptotagmin IJournal of Biological Chemistry, 2002
- Gangliosides are the binding substances in neural cells for tetanus and botulinum toxins in miceBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1999
- Clostridial Toxins as Therapeutic Agents: Benefits of Nature's Most Toxic ProteinsAnnual Review of Microbiology, 1999
- The high‐affinity binding of Clostridium botulinum type B neurotoxin to synaptotagmin II associated with gangliosides GT1b/GD1aFEBS Letters, 1996
- Botulinum neurotoxins serotypes A and E cleave SNAP‐25 at distinct COOH‐terminal peptide bondsFEBS Letters, 1993
- Exo-endocytotic recycling of synaptic vesicles in developing processes of cultured hippocampal neuronsThe Journal of cell biology, 1992
- Identification of a transmembrane glycoprotein specific for secretory vesicles of neural and endocrine cells.The Journal of cell biology, 1985
- Interaction between Clostridium botulinum neurotoxin and gangliosidesBiochimica et Biophysica Acta (BBA) - General Subjects, 1980