期刊
JOURNAL OF CELL BIOLOGY
卷 162, 期 7, 页码 1293-1303出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200305098
关键词
synaptotagmin; synaptobrevin; clostridial neurotoxin; neurotoxin receptor; gangliosides
类别
资金
- NIAID NIH HHS [AI42226] Funding Source: Medline
- NIGMS NIH HHS [GM 56827, R01 GM056827] Funding Source: Medline
- NIMH NIH HHS [R01 MH061876, MH61876] Funding Source: Medline
Botulinum neurotoxins (BoNTs) cause botulism by entering neurons and cleaving proteins that mediate neurotransmitter release; disruption of exocytosis results in paralysis and death. The receptors for BoNTs are thought to be composed of both proteins and gangliosides; however, protein components that mediate toxin entry have not been identified. Using gain-of-function and loss-of-function approaches, we report here that the secretory vesicle proteins, synaptotagmins (syts) I and II, mediate the entry of BoNT/B (but not BoNT/A or E) into PC12 cells. Further, we demonstrate that BoNT/B entry into PC12 cells and rat diaphragm motor nerve terminals was activity dependent and can be blocked using fragments of syt II that contain the BoNT/B-binding domain. Finally, we show that syt II fragments, in conjunction with gangliosides, neutralized BoNT/B in intact mice. These findings establish that syts I and II can function as protein receptors for BoNT/B.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据