Fig. 1. Schematic model of post-translational modification and subcellular targeting of GAD65. Newly synthesized hydrophilic and soluble GAD65 (F1) undergoes an irreversible hydrophobic modification in the cytosol (Step A). The resulting hydrophobic GAD65 (F2) reversibly associates with Golgi membranes. In Golgi membranes, the protein undergoes palmitoylation (Step B) catalyzed by a palmitoyl transferase (PAT). The palmitoylated protein (F3) is targeted out of the Golgi compartment and to a pathway to synaptic vesicles and presynaptic termini in neurons and synaptic-like microvesicles in pancreatic β cells.