Copper that is taken up from the blood by hCTR1 in the basolateral membrane enters the normal pathway for copper incorporation. A recent interesting examination of copper homeostasis in Drosophila showed that the Ctr1B, one of several copper import proteins in the fly, was apically located in fly intestinal cells ( 30 ).

Once released, copper binds to cytosolic proteins (brown semicircles) and is also delivered to copper chaperones and cytochrome C oxidase in mitochondria, as well as to Cu-ATPases in the secretory pathway. Cu-ATPase ATP7A transports copper to vesicles, which then fuse with the basolateral membrane and copper is released into the blood.

When intracellular Cu loads are high, ATP7A traffics to the basolateral membrane and transports Cu + into portal circulation. ATP7B sequesters Cu in vesicles, presumably to buffer cytosolic Cu levels or deliver Cu to yet-to-be-identified Cu-dependent enzymes located in the vesicles.

ATP7B is usually found in the apical membrane of the polarized cells and ATP7A in the basolateral membrane. Copper excretion into the bile is the main function of ATP7B in the liver [8], while ATP7A facilitates copper uptake in the intestine, transporting copper from the enterocytes into the bloodstream. Distinct functions of ATP7B and ATP7A in ...