Copper does not alter the intracellular distribution of ATP7B, a copper-transporting ATPase.

Abstract

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, the mechanism of biliary copper excretion has not been fully clarified. We examined the effect of copper on the intracellular localization of the Wilson disease gene product (ATP7B) and green fluorescent protein (GFP)-tagged ATP7B in a human hepatoma cell line (Huh7). The intracellular organelles were visualized by fluorescence microscopy. GFP-ATP7B colocalized with late endosome markers, but not with endoplasmic reticulum, Golgi, or lysosome markers 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 copper-loaded states. ATP7B seems to translocate copper from the cytosol to the late endosomal lumen, thus participating in biliary copper excretion via lysosomes.

• Authors: M Harada, S Sakisaka, T Kawaguchi, R Kimura, E Taniguchi, H Koga, S Hanada, S Baba, K Furuta, R Kumashiro, T Sugiyama, M Sata
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 275 Issue 3 Pg. 871-6 (Sep 07 2000) ISSN: 0006-291X [Print] United States
• PMID: 10973814 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 Academic Press.

Chemical References

• Antigens, CD
• Biomarkers
• Carrier Proteins
• Cation Transport Proteins
• Lysosome-Associated Membrane Glycoproteins
• Membrane Glycoproteins
• Recombinant Fusion Proteins
• Propidium
• Copper
• Cathepsin D
• Adenosine Triphosphatases
• ATP7B protein, human
• Copper-Transporting ATPases

Topics

• Adenosine Triphosphatases (genetics, metabolism)
• Antigens, CD (analysis)
• Biological Transport (drug effects)
• Biomarkers
• Carcinoma, Hepatocellular (enzymology, pathology)
• Carrier Proteins (genetics, metabolism)
• Cathepsin D (analysis)
• Cation Transport Proteins
• Copper (metabolism, pharmacology)
• Copper-Transporting ATPases
• Endosomes (drug effects, metabolism)
• Fluorescent Antibody Technique
• Hepatolenticular Degeneration (enzymology, genetics)
• Humans
• Lysosome-Associated Membrane Glycoproteins
• Lysosomes (drug effects, metabolism)
• Membrane Glycoproteins (analysis)
• Microscopy, Confocal
• Propidium
• Recombinant Fusion Proteins (metabolism)
• Transfection
• Tumor Cells, Cultured