SV2 is the protein receptor for botulinum neurotoxin A
SV2 is the protein receptor for botulinum neurotoxin A
复制标题
DOI：
10.1126/science.1123654
复制
发表时间：
2006-04-28
期刊：
影响因子：
56.9
通讯作者：
Chapman, ER
中科院分区：
文献类型：
--
作者：
Dong, M;Yeh, F;Chapman, ER
广泛使用的肉毒杆菌神经毒素A（BoNT/A）如何识别和进入神经元还知之甚少。我们发现BoNT/A通过与突触囊泡蛋白SV 2（亚型A、B和C）结合进入神经元。含有毒素相互作用结构域的SV 2片段抑制BoNT/A与神经元的结合。BoNT/A与SV 2A和SV 2B敲除海马神经元的结合被消除，并通过表达SV 2A、SV 2B或SV 2C而恢复。在PC 12和Neuro-2a细胞中SV 2表达的减少也抑制BoNT/A的进入，这可以通过表达SV 2同种型来恢复。最后，缺乏SV 2同种型（SV 2B）的小鼠对BoNT/A的敏感性降低。因此，SV 2充当BoNT/A的蛋白质受体。
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.