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FEBS Lett. 2006 Apr 3;580(8):2011-4. Epub 2006 Mar 7.

The synaptic vesicle protein 2C mediates the uptake of botulinum neurotoxin A into phrenic nerves.

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Institute of Biochemistry, OE 4310, Carl-Neuberg-Strasse 1, Medical School Hannover, 30623 Hannover, Germany.


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.

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