突触囊泡蛋白2是肉毒杆菌神经毒素A的蛋白质受体。

SV2 is the protein receptor for botulinum neurotoxin A.

作者信息

Dong Min, Yeh Felix, Tepp William H, Dean Camin, Johnson Eric A, Janz Roger, Chapman Edwin R

机构信息

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

出版信息

Science. 2006 Apr 28;312(5773):592-6. doi: 10.1126/science.1123654. Epub 2006 Mar 16.

DOI:10.1126/science.1123654

PMID:16543415

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.

摘要

广泛使用的A型肉毒杆菌神经毒素（BoNT/A）如何识别并进入神经元，目前尚不清楚。我们发现BoNT/A通过与突触囊泡蛋白SV2（A、B和C亚型）结合进入神经元。携带毒素相互作用结构域的SV2片段可抑制BoNT/A与神经元结合。BoNT/A与SV2A和SV2B基因敲除的海马神经元的结合被消除，而通过表达SV2A、SV2B或SV2C可恢复结合。PC12和Neuro-2a细胞中SV2表达的降低也抑制了BoNT/A的进入，通过表达SV2亚型可恢复。最后，缺乏一种SV2亚型（SV2B）的小鼠对BoNT/A的敏感性降低。因此，SV2作为BoNT/A的蛋白受体发挥作用。