Clostridial Neurotoxins and the Blockade of Neurotransmitter Release

Recently, Sollner and colleagues (Sollner etal., 1993 a, b] have shown that VAMP, SNAP-25 and syntaxin, together with a group of cytosolic proteins (NSF, a- and y-SNAP), form a 20S protein complex involved in the docking and fusion of SSV with the presynaptic membrane (Rothman, 1994 Sollner, 1995). 

SNAP-25 and syntaxin form a stoichiometric complex. This complex can bind one molecule of VAMP with high affinity. This trimeric SNARE complex is stable in sodium dodecylsulfate (Chapman et al., 1994 Hayashi etal., 1994, 1995). In the process of neuroexocytosis, SNARE complex formation precedes the recruitment of cytosolic and membrane protein components required for fusion of the lipid bilayers (Rothman, 1994 Sollner, 1995). It is likely that NSF-mediated hydrolysis of ATP provides energy for priming the neuroexocytotic apparatus. The primed system is now ready to trigger exocytosis upon calcium influx into the synapse. It is not yet established if the last step of neurotransmitter release takes place via a fusion pore or through a complete membrane fusion with lipid intermixing (Monk and Fernandez, 1994 Bruns and John, 1996). 

Cleavage of VAMP and syntaxin by TeTx, BoNT/B, D, F, G and C leads to the release of a large part of the target molecule into the cytosol. These fragments, as well the fragments of SNAP-25 gener- 

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