Fusion complex formation protects synaptobrevin against proteolysis by tetanus toxin light chain.

The clostridial neurotoxin, tetanus toxin, is a Zn(2+)-dependent protease which inhibits neurotransmitter exocytosis by selective cleavage of the synaptic vesicle protein, synaptobrevin. Synaptobrevin is thought to serve as a receptor for two neuronal plasma membrane proteins, syntaxin and SNAP-25, which in the presence of non-hydrolyzable ATP analogs form a 20 S fusion complex with the soluble fusion proteins NSF and alpha-SNAP. Here we show that synaptobrevin, when in this 20 S complex, or its 7 S precursor, is protected against proteolysis by the enzymatically active tetanus toxin light chain. Our data define distinct pools of synaptobrevin, which provide markers of different steps of vesicle/plasma membrane interaction.