Abstract

Tetanus toxin is internalized by way of acidic endosomes. Monensin and bafilomycin, agents which disrupt the endosomal pH gradient, protect neurons against the effects of the toxin. In synaptic terminals poisoned with tetanus toxin, there are twice as many synaptic vesicles aligned at the active zone as there are in control preparations. This finding strengthens the notion that the toxin acts by preventing vesicle fusion with the presynaptic membrane. Tetanus toxin acts with a different time course on inhibitory and excitatory synapses. Following exposure to tetanus toxin, inhibitory synapses are blocked more quickly and recover more slowly than excitatory synapses. Neurotransmitter release from neuronal cell cultures has proven to be a reliable assay for the efficacy of anthrax toxin-tetanus toxin fusion proteins.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Intramural Research (Z01)
Project #
1Z01HD000704-09
Application #
3778567
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
Eunice Kennedy Shriver National Institute of Child Health & Human Development
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Keller, James E; Cai, Fang; Neale, Elaine A (2004) Uptake of botulinum neurotoxin into cultured neurons. Biochemistry 43:526-32
Neale, Elaine A (2003) Moving across membranes. Nat Struct Biol 10:2-3
Neale, Edward J; Elliott, David J S; Hunter, Malcolm et al. (2003) Evidence for intersubunit interactions between S4 and S5 transmembrane segments of the Shaker potassium channel. J Biol Chem 278:29079-85
Goodnough, Michael C; Oyler, George; Fishman, Paul S et al. (2002) Development of a delivery vehicle for intracellular transport of botulinum neurotoxin antagonists. FEBS Lett 513:163-8
Keller, J E; Neale, E A (2001) The role of the synaptic protein snap-25 in the potency of botulinum neurotoxin type A. J Biol Chem 276:13476-82
Neale, E A; Bowers, L M; Jia, M et al. (1999) Botulinum neurotoxin A blocks synaptic vesicle exocytosis but not endocytosis at the nerve terminal. J Cell Biol 147:1249-60
Williamson, L C; Bateman, K E; Clifford, J C et al. (1999) Neuronal sensitivity to tetanus toxin requires gangliosides. J Biol Chem 274:25173-80
Keller, J E; Neale, E A; Oyler, G et al. (1999) Persistence of botulinum neurotoxin action in cultured spinal cord cells. FEBS Lett 456:137-42