INHIBITION OF NEUROTRANSMITTER RELEASE BY CLOSTRIDIAL NEUROTOXINS CORRELATES WITH SPECIFIC PROTEOLYSIS OF SYNAPTOSOMAL PROTEINS

Rat brain synaptosomes were used to study the effect of several clostr idial neurotoxins on the neurotransmitter release. In this system the blockade of transmitter release correlated with the proteolytic activi ty of the toxins. Blockade of glutamate release was linked to selectiv e proteolysis of one of the following synaptic proteins: synaptobrevin (BoNT/D, BoNT/F); SNAP-25 (BoNT/A, BoNT/E), or HPC-1/syntaxin (BoNT/C 1). All the toxins used had an inhibitory effect on synaptosomes with the exception of BoNT/E BoNT/F cleaved synaptobrevin in permeabilized synaptosomes but failed to produce the same effect on intact synaptoso mes.