Fig. 7. Schematic model of SNARE complex states before and during exocytosis. This model is based on previous data from adrenal chromaffin cells (Xu et al., 1998; Xu et al., 1999b), synapses (Hua and Charlton, 1999), liposome fusion (Weber et al., 2000) and the data presented in this paper. In this model, secretory vesicles initially associate with the plasma membrane via a loose SNARE complex in which the SNAREs are sensitive to clostridial neurotoxins. Disassembly of cis SNARE complexes may be important prior to exocytosis to free SNAREs for assembly into the initial trans complex (Graham and Burgoyne, 2000; Xu et al., 1999a). Conversion to a ‘tight’ complex resistant to tetanus toxin precedes fusion, and fusion itself is driven by a complex that is fully toxin-resistant but not zipped up into the stable complex. The formation of the stable SNARE complex occurs only after full fusion has been completed and then it be can disassembled by the action of -SNAP and NSF.