Gene duplication and neo-functionalization in the evolutionary and functional divergence of the metazoan copper transporters Ctr1 and Ctr2.

The Journal of Biological Chemistry
Brandon LogemanD J Thiele

Abstract

Copper is an essential element for proper organismal development and is involved in a range of processes, including oxidative phosphorylation, neuropeptide biogenesis, and connective tissue maturation. The copper transporter (Ctr) family of integral membrane proteins is ubiquitously found in eukaryotes and mediates the high-affinity transport of Cu+ across both the plasma membrane and endomembranes. Although mammalian Ctr1 functions as a Cu+ transporter for Cu acquisition and is essential for embryonic development, a homologous protein, Ctr2, has been proposed to function as a low-affinity Cu transporter, a lysosomal Cu exporter, or a regulator of Ctr1 activity, but its functional and evolutionary relationship to Ctr1 is unclear. Here we report a biochemical, genetic, and phylogenetic comparison of metazoan Ctr1 and Ctr2, suggesting that Ctr2 arose over 550 million years ago as a result of a gene duplication event followed by loss of Cu+ transport activity. Using a random mutagenesis and growth selection approach, we identified amino acid substitutions in human and mouse Ctr2 proteins that support copper-dependent growth in yeast and enhance copper accumulation in Ctr1-/- mouse embryonic fibroblasts. These mutations revert Ctr2...Continue Reading

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Citations

Jun 7, 2018·American Journal of Physiology. Cell Physiology·Tohru FukaiJack H Kaplan
May 19, 2018·International Journal of Molecular Sciences·Yu-Hsuan LaiHelen H W Chen
Sep 26, 2020·The Journal of Membrane Biology·Taniya MandalArnab Gupta
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Jan 8, 2021·Nanotechnology, Science and Applications·Ekaterina A SkomorokhovaEkaterina Yu Ilyechova
Jul 23, 2021·Journal of Trace Elements in Medicine and Biology : Organ of the Society for Minerals and Trace Elements (GMS)·Yimin GongXiaoli Yang
Oct 23, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Vinit C ShanbhagMichael J Petris

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