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Trafficking of the copper-ATPases, ATP7A and ATP7B: role in copper homeostasis.
Arch Biochem Biophys. 2007 Jul 15; 463(2):149-67.AB

Abstract

Copper is essential for human health and copper imbalance is a key factor in the aetiology and pathology of several neurodegenerative diseases. The copper-transporting P-type ATPases, ATP7A and ATP7B are key molecules required for the regulation and maintenance of mammalian copper homeostasis. Their absence or malfunction leads to the genetically inherited disorders, Menkes and Wilson diseases, respectively. These proteins have a dual role in cells, namely to provide copper to essential cuproenzymes and to mediate the excretion of excess intracellular copper. A unique feature of ATP7A and ATP7B that is integral to these functions is their ability to sense and respond to intracellular copper levels, the latter manifested through their copper-regulated trafficking from the transGolgi network to the appropriate cellular membrane domain (basolateral or apical, respectively) to eliminate excess copper from the cell. Research over the last decade has yielded significant insight into the enzymatic properties and cell biology of the copper-ATPases. With recent advances in elucidating their localization and trafficking in human and animal tissues in response to physiological stimuli, we are progressing rapidly towards an integrated understanding of their physiological significance at the level of the whole animal. This knowledge in turn is helping to clarify the biochemical and cellular basis not only for the phenotypes conferred by individual Menkes and Wilson disease patient mutations, but also for the clinical variability of phenotypes associated with each of these diseases. Importantly, this information is also providing a rational basis for the applicability and appropriateness of certain diagnostic markers and therapeutic regimes. This overview will provide an update on the current state of our understanding of the localization and trafficking properties of the copper-ATPases in cells and tissues, the molecular signals and posttranslational interactions that govern their trafficking activities, and the cellular basis for the clinical phenotypes associated with disease-causing mutations.

Authors+Show Affiliations

Centre for Cellular and Molecular Biology, School of Life and Environmental Sciences, 221 Burwood Highway, Burwood, Vic. 3125, Australia. sharonl@deakin.edu.auNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

17531189

Citation

La Fontaine, Sharon, and Julian F B. Mercer. "Trafficking of the copper-ATPases, ATP7A and ATP7B: Role in Copper Homeostasis." Archives of Biochemistry and Biophysics, vol. 463, no. 2, 2007, pp. 149-67.
La Fontaine S, Mercer JF. Trafficking of the copper-ATPases, ATP7A and ATP7B: role in copper homeostasis. Arch Biochem Biophys. 2007;463(2):149-67.
La Fontaine, S., & Mercer, J. F. (2007). Trafficking of the copper-ATPases, ATP7A and ATP7B: role in copper homeostasis. Archives of Biochemistry and Biophysics, 463(2), 149-67.
La Fontaine S, Mercer JF. Trafficking of the copper-ATPases, ATP7A and ATP7B: Role in Copper Homeostasis. Arch Biochem Biophys. 2007 Jul 15;463(2):149-67. PubMed PMID: 17531189.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Trafficking of the copper-ATPases, ATP7A and ATP7B: role in copper homeostasis. AU - La Fontaine,Sharon, AU - Mercer,Julian F B, Y1 - 2007/05/07/ PY - 2007/02/02/received PY - 2007/04/18/revised PY - 2007/04/18/accepted PY - 2007/5/29/pubmed PY - 2007/8/19/medline PY - 2007/5/29/entrez SP - 149 EP - 67 JF - Archives of biochemistry and biophysics JO - Arch Biochem Biophys VL - 463 IS - 2 N2 - Copper is essential for human health and copper imbalance is a key factor in the aetiology and pathology of several neurodegenerative diseases. The copper-transporting P-type ATPases, ATP7A and ATP7B are key molecules required for the regulation and maintenance of mammalian copper homeostasis. Their absence or malfunction leads to the genetically inherited disorders, Menkes and Wilson diseases, respectively. These proteins have a dual role in cells, namely to provide copper to essential cuproenzymes and to mediate the excretion of excess intracellular copper. A unique feature of ATP7A and ATP7B that is integral to these functions is their ability to sense and respond to intracellular copper levels, the latter manifested through their copper-regulated trafficking from the transGolgi network to the appropriate cellular membrane domain (basolateral or apical, respectively) to eliminate excess copper from the cell. Research over the last decade has yielded significant insight into the enzymatic properties and cell biology of the copper-ATPases. With recent advances in elucidating their localization and trafficking in human and animal tissues in response to physiological stimuli, we are progressing rapidly towards an integrated understanding of their physiological significance at the level of the whole animal. This knowledge in turn is helping to clarify the biochemical and cellular basis not only for the phenotypes conferred by individual Menkes and Wilson disease patient mutations, but also for the clinical variability of phenotypes associated with each of these diseases. Importantly, this information is also providing a rational basis for the applicability and appropriateness of certain diagnostic markers and therapeutic regimes. This overview will provide an update on the current state of our understanding of the localization and trafficking properties of the copper-ATPases in cells and tissues, the molecular signals and posttranslational interactions that govern their trafficking activities, and the cellular basis for the clinical phenotypes associated with disease-causing mutations. SN - 0003-9861 UR - https://www.unboundmedicine.com/medline/citation/17531189/Trafficking_of_the_copper_ATPases_ATP7A_and_ATP7B:_role_in_copper_homeostasis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0003-9861(07)00210-X DB - PRIME DP - Unbound Medicine ER -