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

被引：249

作者：

Mahrhold, S

Rummel, A

Bigalke, H

Davletov, B

Binz, T

机构：

[1] Hannover Med Sch, Inst Biochem, D-30623 Hannover, Germany

[2] Hannover Med Sch, Inst Toxicol, D-30623 Hannover, Germany

[3] MRC, Mol Biol Lab, Cambridge CB2 2QH, England

来源：

FEBS LETTERS | 2006年 / 580卷 / 08期

基金：

英国医学研究理事会;

关键词：

botulinum neurotoxin; ganglioside; phrenic nerve; protein receptor; SV2;

D O I：

10.1016/j.febslet.2006.02.074

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2011 / 2014

页数：4