JCB logo
Avanti Polar Lipids
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 22 September 2003. doi:10.1083/jcb.200305098
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow Supplemental Material Index
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dong, M.
Right arrow Articles by Chapman, E. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dong, M.
Right arrow Articles by Chapman, E. R.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© The Rockefeller University Press, 0021-9525/2003/9/1293 $5.00
The Journal of Cell Biology, Volume 162, Number 7, 1293-1303

Article

 Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells

Min Dong1, David A. Richards1, Michael C. Goodnough2,3, William H. Tepp2, Eric A. Johnson2 and Edwin R. Chapman1

1 Department of Physiology and the Neuroscience Training Program, University of Wisconsin, Madison, Madison, WI 53706
2 Department of Food Microbiology and Toxicology, University of Wisconsin, Madison, Madison, WI 53706
3 Metabiologics, Inc., Madison, WI 53719

Address correspondence to E.R. Chapman, Dept. of Physiology, SMI 129, University of Wisconsin, Madison, 1300 University Ave., Madison, WI 53706. Tel.: (608) 263-1762. Fax: (608) 265-5512. email: chapman{at}physiology.wisc.edu

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.

Key Words: synaptotagmin; synaptobrevin; clostridial neurotoxin; neurotoxin receptor; gangliosides

The online version of this article includes supplemental material.

Abbreviations used in this paper: BoNT, botulinum neurotoxin; CNT, clostridial neurotoxin; syb, synaptobrevin; syt, synaptotagmin; TeNT, tetanus neurotoxin.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article

How to block botox
Alan W. Dove
J. Cell Biol. 2003 162: 1178-1179. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents