Cellular Copper Transport and Metabolism

Harris, Edward D.

doi:10.1146/annurev.nutr.20.1.291

Cited by 279 publications

(174 citation statements)

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“…Thus cells have evolved a homeostatic pathway for the uptake, distribution, and sequestration of copper such that the essential cellular requirements for copper can be achieved while minimizing its toxic potential. Studies in bakers' yeast, Saccharomyces cerevisiae, facilitated the discovery of many of the components of the copper homeostatic pathway, and these proteins are strongly conserved among species extending all the way to mammals (3,8,9).…”

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Drosophila Ctr1A Functions as a Copper Transporter Essential for Development

Turski¹,

Thiele

2007

Journal of Biological Chemistry

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Copper is an essential trace element required by all aerobic organisms as a cofactor for enzymes involved in normal growth, development, and physiology. Ctr1 proteins are members of a highly conserved family of copper importers responsible for copper uptake across the plasma membrane. Mice lacking Ctr1 die during embryogenesis from widespread developmental defects, demonstrating the need for adequate copper acquisition in the development of metazoan organisms via as yet uncharacterized mechanisms. Whereas the fruit fly, Drosophila melanogaster, expresses three Ctr1 genes, ctr1A, ctr1B, and ctr1C, little is known about their protein isoform-specific roles. Previous studies demonstrated that Ctr1B localizes to the plasma membrane and is not essential for development unless flies are severely copper-deficient or are subjected to copper toxicity. Here we demonstrate that Ctr1A also resides on the plasma membrane and is the primary Drosophila copper transporter. Loss of Ctr1A results in copper-remedial developmental arrest at early larval stages. Ctr1A mutants are deficient in the activity of copper-dependent enzymes, including cytochrome c oxidase and tyrosinase. Amidation of Phe-Met-Arg-Pheamides, a group of cardiomodulatory neuropeptide hormones that are matured via the action of peptidylglycine ␣-hydroxylating monooxygenase, is defective in neuroendocrine cells of Ctr1A mutant larvae. Moreover, both the Phe-Met-Arg-Pheamide maturation and heart beat rate defects observed in Ctr1A mutant larvae can be partially rescued by exogenous copper. These studies establish clear physiological distinctions between two Drosophila plasma membrane copper transport proteins and demonstrate that copper import by Ctr1A is required to drive neuropeptide maturation during normal growth and development.

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Drosophila Ctr1A Functions as a Copper Transporter Essential for Development

Turski¹,

Thiele

2007

Journal of Biological Chemistry

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“…The copper homeostasis network has been primarily described in the yeast Saccharomyces cerevisiae (for reviews see Refs. [7][8][9], and its components are widely conserved among eukaryotes.…”

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The Arabidopsis Copper Transporter COPT1 Functions in Root Elongation and Pollen Development

Sancenón

Puig

Mateu‐Andrés

et al. 2004

Journal of Biological Chemistry

252

197

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Copper plays a dual role in aerobic organisms, as both an essential and a potentially toxic element. To ensure copper availability while avoiding its toxic effects, organisms have developed complex homeostatic networks to control copper uptake, distribution, and utilization. In eukaryotes, including yeasts and mammals, high affinity copper uptake is mediated by the Ctr family of copper transporters. This work is the first report on the physiological function of copper transport in Arabidopsis thaliana. We have studied the expression pattern of COPT1 in transgenic plants expressing a reporter gene under the control of the COPT1 promoter. The reporter gene is highly expressed in embryos, trichomes, stomata, pollen, and root tips. The involvement of COPT1 in copper acquisition was investigated in CaMV35S::COPT1 antisense transgenic plants. Consistent with a decrease in COPT1 expression and the associated copper deprivation, these plants exhibit increased mRNA levels of genes that are down-regulated by copper, decreased rates of 64 Cu uptake by seedlings and reduced steady state levels of copper as measured by atomic absorption spectroscopy in mature leaves. Interestingly, COPT1 antisense plants also display dramatically increased root length, which is completely and specifically reversed by copper addition, and an increased sensitivity to growth inhibition by the copper-specific chelator bathocuproine disulfonic acid. Furthermore, COPT1 antisense plants exhibit pollen development defects that are specifically reversed by copper. Taken together, these studies reveal striking plant growth and development roles for copper acquisition by high affinity copper transporters.

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“…The key role in copper distribution in human cells belongs to the copper-transporting ATPases ATP7A and ATP7B (Menkes disease and Wilson's disease proteins, respectively). These large polytopic membrane proteins utilize the energy of ATP hydrolysis to transport copper from the cytosol into the lumen of the secretory compartment where copper can be incorporated into various copper-dependent enzymes (1). When intracellular copper exceeds a certain level, the copper-transporting ATPases traffic to the plasma membrane where they export excess copper out of the cell (2,3).…”

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confidence: 99%