Tetanus toxin and botulinum toxins are neurotoxins which have similar structures and modes of action. The toxicity of both of these toxins results from proteolytic cleavage of so-called SNARE proteins. While inactivated forms of the proteins are used as vaccines, botulinum toxin is being used more as a therapeutic against disease involving muscle spasms. The work on this project is directed toward defining how tetanus toxin action blocks the targeting and fusion of intracellular transport vesicles. As a model system, tetanus toxin action is being studied for CHO cells which lack receptor for the toxin using a chimera of tetanus enzymatic domain and anthrax receptor domain. While the chimera is cytotoxic for CHO cells it is not active toward the expected SNARE protein, VAMP. Efforts are underway to identify isoforms of VAMP in CHO cells which may explain this phenomenon.
