Wilson's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Wilson's Disease, including details on treatment, causes, symptoms, medication.

Intracellular targeting of copper-transporting ATPase ATP7A in a normal and Atp7b / kidney.

Linz R, Barnes NL, Zimnicka AM, Kaplan JH, Eipper B, Lutsenko S

Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR 97239, USA.

Kidneys regulate their copper content more effectively than many other organs in diseases of copper deficiency or excess. We demonstrate that two copper-transporting ATPases, ATP7A and ATP7B, contribute to this regulation. ATP7A is expressed, to a variable degree, throughout the kidney and shows age-dependent intracellular localization. In 2-wk-old mice, ATP7A is located in the vicinity of the basolateral membrane, whereas in 20-wk-old mice, ATP7A is predominantly in intracellular vesicles. Acute elevation of serum copper, via intraperitoneal injection, results in the in vivo redistribution of ATP7A from intracellular compartments toward the basolateral membrane, illustrating a role for ATP7A in renal response to changes in copper load. Renal copper homeostasis also requires functional ATP7B, which is coexpressed with ATP7A in renal cells of proximal and distal origin. The kidneys of Atp7b(-/-) mice, an animal model of Wilson disease, show metabolic alterations manifested by the appearance of highly fluorescent deposits; however, in marked contrast to the liver, renal copper is not significantly elevated. The lack of notable copper accumulation in the Atp7b(-/-) kidney is likely due to the compensatory export of copper by ATP7A. This interpretation is supported by the predominant localization of ATP7A at the basolateral membrane of Atp7b(-/-) cortical tubules. Our results suggest that both Cu-ATPases regulate renal copper, with ATP7A playing a major role in exporting copper via basolateral membranes and protecting renal tissue against copper overload.

Published 10 January 2008 in Am J Physiol Renal Physiol, 294(1): F53-61.
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