Figure 8.

Model illustrating the sites of action for α-SNAP and NSF in the SNARE conformational cycle during exocytosis. A-SNAP binds with high affinity to cis-SNARE complexes and with lower affinity to free syntaxin. Under normal circumstances, the equilibrium is shifted toward the dissociated part of the cycle, with the steady-state concentration of both cis-complexes and α-SNAP/syntaxin complexes being low. However, if the SNAP–NSF system is imbalanced due to overexpression of α-SNAP or down-regulation/inhibition of NSF, free syntaxin rapidly becomes rate limiting, resulting in an inhibition of exocytosis. Please note that free syntaxin is organized in clusters (not shown in the figure), and it is not known whether α-SNAP exhibits any preference for free versus clustered syntaxin. See text for details.