gun" so that, once vesicle fusion is triggered, the process takes place spontaneously and at optimum velocity. A comparable process takes place in muscles, in which the myosin heads must first hydrolyze ATP in order to adapt the necessary conformation for interaction with actin and the subsequent power stroke to occur. Regulatory effects on exocytosis Regulation via SNAP-25 palmitoylation The Q-SNARE protein Synaptosomal-associated protein 25 (SNAP-25) is composed of two α-helical domains connected by a random coil linker. The random coil linker region is most notable for its four cysteine residues. The α-helical domains combine with those of both syntaxin and synaptobrevin (also known as vesicle associated membrane protein or VAMP) to form the 4-α-helix coiled-coil SNARE complex critical to efficient exocytosis. While syntaxin and synaptobrevin both contain transmembrane domains which allow for docking with target and vesicle membranes respectively, SNAP-25 relies on the palmitoylation of cysteine residues found in its random coil region for docking to the target membrane. Some studies have suggested that association with syntaxin via SNARE interactions precludes the need for such docking mechanisms. Syntaxin knockdown studies however, failed to show a decrease in membrane bound SNAP-25 suggesting alternate docking means exist. The covalent bonding of fatty acid chains to SNAP-25 via thioester linkages with one or more cysteine residues therefore, provides for regulation of docking and ultimately SNARE mediated exocytosis. This process is mediated by a specialized enzyme called DHHC palmitoyl transferase. The cysteine rich domain of SNAP-25 has also been shown to weakly associate with the plasma membrane possibly allowing it to be localized near the enzyme for subsequent palmitoylation. The reverse of this process is carried out by another enzyme called palmitoyl protein thioesterase (see figure). The availability of SNAP-25 in the SNARE complex is also theorized to possibly be spatially regulated via localization of lipid microdomains in the target membrane. Palmitoylated cysteine residues could be localized to the desired target membrane region via a favorable lipid environment (possibly cholesterol rich) complementary to the fatty acid chains bonded to the cysteine residues of SNAP-25. SNAP-25 regulation of voltage-gated Ca2+ channels in neuronal axon terminals As an action potential reaches the axon terminal, depolarization events stimulate the opening of voltage-gated calcium channels (VGCCs) allowing the rapid influx of calcium down its electrochemical gradient. Calcium goes on to stimulate exocytosis via binding with synaptotagmin 1. SNAP-25 however, has been shown to negatively regulate VGCC function