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Hepatic copper-transporting ATPase ATP7B: function and inactivation at the molecular and cellular level

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Abstract

Copper-transporting ATPase ATP7B (Wilson disease protein) is a member of the P-type ATPase family with characteristic domain structure and distinct ATP-binding site. ATP7B plays a central role in the regulation of copper homeostasis in the liver by delivering copper to the secretory pathway and mediating export of excess copper into the bile. The dual function of ATP7B in hepatocytes is coupled with copper-dependent intracellular relocalization of the transporter. The final destination of ATP7B in hepatocytes during the copper-induced trafficking process is still under debate. We show the results of immunocytochemistry experiments in polarized HepG2 cells that support the model in which elevated copper induces trafficking of ATP7B to sub-apical vesicles, and transiently to the canalicular membrane. In Atp7b -/- mice, an animal model of Wilson disease, both copper delivery to the trans-Golgi network and copper export into the bile are disrupted despite large accumulation of copper in the cytosol. We review the biochemical and physiological changes associated with Atp7b inactivation in mouse liver and discuss the pleiotropic consequences of the common Wilson disease mutation, His1069Gln.

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Acknowledgements

This work was supported by the National Institute of Health grants F31-NS047963 to M.Y.B. (M.Min) and PO1 GM 067166 and R01DK071865 to S.L.

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  1. Department of Biochemistry and Molecular Biology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Mee Y. Bartee & Svetlana Lutsenko

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Correspondence to Svetlana Lutsenko.

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Bartee, M.Y., Lutsenko, S. Hepatic copper-transporting ATPase ATP7B: function and inactivation at the molecular and cellular level. Biometals 20, 627–637 (2007). https://doi.org/10.1007/s10534-006-9074-3

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