Journal
FEBS LETTERS
Volume 580, Issue 8, Pages 2011-2014Publisher
WILEY
DOI: 10.1016/j.febslet.2006.02.074
Keywords
botulinum neurotoxin; ganglioside; phrenic nerve; protein receptor; SV2
Funding
- MRC [MC_U105178791] Funding Source: UKRI
- Medical Research Council [MC_U105178791] Funding Source: Medline
- Medical Research Council [MC_U105178791] Funding Source: researchfish
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Botulinum neurotoxins (BoNTs) inhibit neurotransmitter release by selectively cleaving core components of the vesicular fusion machinery. The synaptic vesicle proteins Synaptotagmin-I and -II act as receptors for BoNT/B and BoNT/G. Here we show that BoNT/A also interacts with a synaptic vesicle protein, the synaptic vesicle glycoprotein 2C (SV2C), but not with the homologous proteins SV2A and SV2B. Binding of BoNT/A occurs at the membrane juxtaposed region preceding transmembrane domain 8. A peptide comprising the intravesicular domain between transmembrane domains 7 and 8 specifically reduces the neurotoxicity of BoNT/A at phrenic nerve preparations demonstrating the physiological relevance of this interaction. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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