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Review
. 2011 Mar;2(2):129-37.
doi: 10.3945/an.110.000273. Epub 2011 Mar 10.

Advances in the understanding of mammalian copper transporters

Affiliations
Review

Advances in the understanding of mammalian copper transporters

Yanfang Wang et al. Adv Nutr. 2011 Mar.

Abstract

Copper (Cu) is an essential micronutrient. Its ability to exist in 2 oxidation states (Cu(1+) and Cu(2+)) allows it to function as an enzymatic cofactor in hydrolytic, electron transfer, and oxygen utilization reactions. Cu transporters CTR1, ATP7A, and ATP7B play key roles in ensuring that adequate Cu is available for Cu-requiring processes and the prevention of excess Cu accumulation within cells. Two diseases of Cu metabolism, Menkes disease and Wilson disease, which are caused by mutations in ATP7A and ATP7B, respectively, exemplify the critical importance of regulating Cu balance in humans. Herein, we review recent studies of the biochemical and cell biological characteristics of CTR1, ATP7A, and ATP7B, as well as emerging roles for Cu in new areas of physiology.

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Conflict of interest statement

Author disclosures: Y. Wang, V. Hodgkinson, S. Zhu, G. A. Weisman, and M. J. Petris, no conflicts of interest.

Figures

Figure 1
Figure 1
Cellular Cu homeostasis. The CTR1 protein functions in Cu uptake. The Cu chaperones COX17 and CCS deliver Cu to CCO and SOD1, respectively. The role of additional Cu chaperones (SCO1 and SCO2) involved in Cu incorporation into CCO is not shown. Cu is delivered to the ATP7A and ATP7B proteins by the ATOX1 Cu chaperone. Both ATP7A and ATP7B transport Cu to Cu dependent enzymes in the TGN. Elevated Cu concentrations stimulate the endocytosis and degradation of CTR1 and the exocytosis of ATP7A and ATP7B to post-Golgi vesicles or the plasma membrane.
Figure 2
Figure 2
Effect of cardiomyocyte specific CTR1 deletion on intestinal and hepatic expression of ATP7A. A schematic model depicting the effect of cardiomyocyte deletion of CTR1 on the expression of ATP7A in intestine and liver. The release of an unknown serum factor in response to cardiac deletion of CTR1 promotes an increase in ATP7A expression in intestinal epithelial cells and hepatocytes. The resulting increase in ATP7A mediated Cu transport into the blood stream across the gastrointestinal tract and from hepatic stores is proposed to increase Cu availability to the heart and peripheral organs.

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