Protein Fragments Protect Against Botulinum Toxin

Researchers have identified the molecules that bind and transport botulinum toxin (BoNT), a bacterial toxin that causes paralysis and is extremely toxic even at very low concentrations.

Previous research had shown that complex cell membrane glycolipids known as gangliosides were involved along with some proteins in the internalization of botulinum toxin. Investigators at the University of Wisconsin (Madison, USA; www.wisc.edu) employed both tissue culture and animal experiments to identify the protein component.

The investigators reported in a study published in the September 29, 2003, issue of the Journal of Cell Biology that they used gain-of-function and loss-of-function approaches to show that the secretory vesicle proteins, synaptotagmins (syts) I and II, mediated the entry of BoNT/B (but not BoNT/A or E) into PC12 tissue culture cells. They also demonstrated that BoNT/B entry into PC12 cells and rat diaphragm motor nerve terminals was activity dependent and could be blocked using fragments of syt II that contain the BoNT/B-binding domain. Finally, they showed that syt II fragments, in conjunction with gangliosides, neutralized BoNT/B in intact mice.

Senior author Dr. Edwin Chapman, professor of physiology at the University of Wisconsin explained, "The fragments are a protective agent, a scavenger, that prevents the toxin from reaching its target.”



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