Figure 1.

Cartoon illustrating the intracellular distribution of ATP7A, ATP7B, and DBH. ATP7A is located in the TGN and transports copper (green balls) into the lumen of this compartment. ATP7B is in vesicles where it sequesters Cu from the cytosol and regulates the amount of cytosolic Cu available to ATP7A. DBH receives its Cu cofactor as it matures within the secretory pathway (most likely from ATP7A). The fraction of DBH is then proteolytically processed. Soluble DBH is sorted to two main destinations. Some soluble DBH and a noncleaved membrane-bound DBH are sorted to secretory granules. In secretory granules, DBH converts DA into NE, which is secreted together with the soluble DBH into the extracellular space in response to extracellular stimuli (regulated secretion). Another fraction of soluble DBH is modified within the secretory pathway and sorted to vesicles, which undergo constitutive trafficking to the plasma membrane. The vesicles fuse with the membrane and export active soluble DBH in the absence of neuronal stimulation (constitutive export).