Wilson's disease is a genetic disorder characterized by the accumulation of
copper in the body due to a defect of biliary copper excretion. However, t
he mechanism of biliary copper excretion has not been fully clarified, We e
xamined the effect of copper on the intracellular localization of the Wilso
n disease gene product (ATP7B) and green fluorescent protein (GFP)-tagged A
TP7B in a human hepatoma cell line (Huh7), The intracellular organelles wer
e visualized by fluorescence microscopy, GFP-ATP7B colocalized with late en
dosome markers, but not with endoplasmic reticulum, Golgi, or lysosome mark
ers in both the steady and copper-loaded states. ATP7B mainly localized at
the perinuclear regions in both states. These results suggest that the main
localization of ATP7B is in the late endosomes in both the steady and copp
er-loaded states. ATP7B seems to translocate copper from the cytosol to the
late endosomal lumen, thus participating in biliary copper excretion via l
ysosomes. (C) 2000 Academic Press.