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Function of Copper Transporters

Function of Copper Transporters. By: Stefano Pineda. Overview. Copper Importers Ctr1 Ctr2 Copper Exporters ADP7A ADP7B. Distribution of copper. Copper Uptake Ctr1. hCtr1. Integral plasma protein. Where is CTR1 Expressed?. Kuo Y et al. PNAS 2001;98:6836-6841.

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Function of Copper Transporters

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  1. Function of Copper Transporters By: Stefano Pineda

  2. Overview • Copper Importers • Ctr1 • Ctr2 • Copper Exporters • ADP7A • ADP7B

  3. Distribution of copper

  4. Copper Uptake Ctr1 hCtr1 • Integral plasma protein

  5. Where is CTR1 Expressed? Kuo Y et al. PNAS 2001;98:6836-6841

  6. CTR1's Role in Development

  7. Intracellular Copper Distribution

  8. Cu-ATPases • Polytopic membrane proteins, transport copper from cytosol to cellular membranes using ATP hydrolysis • Transport copper into biosynthetic pathways for subsequent incorporation into cuproenzymes. • Delivery to Mitochondria, Secretory pathway, and TGN • ATP7A & ATP7B dual function based off intracellular Cu concentration.

  9. Copper Export: Cu-ATPases

  10. Dual Function of Cu-ATPases

  11. ATP7A • Copper exported from enterocytes into the blood stream • Menkes disease – copper export greatly impaired, copper accumulates in intestine, less copper delivered to blood and tissues. • Decreased function of cuproenzymes: connective tissue abnormalities, lack of pigmentation

  12. ATP7B • Liver central organ in copper homeostasis • Export of excess copper out of the body • Hepatic trans-Golgi network contain ATP7B • Receive copper from Atox1 transport it into lumen of the TGN • Incorporated into copper-dependent ferroxidase ceruloplasmin, most abundant copper containing protein in blood • Copper secretion into bile

  13. ATP7A and ATP7B Copper Distribution

  14. In Conclusion • CTR1, and Cu-ATPases essential for tight homeostatic copper control • Mutations that deviate from WT result in Menke's disease and Wilson's disease • Copper transport essential for important physiological processes and development

  15. References Van den Burghe, Peter V. E. and Klomp, Leo W. J. Posttranslational Regulation of Copper Transporters. Journal of Biological Inorganic Chemistry (2010) 15: 37-46 Lutsenko, Svetlana et.al. Function and Regulation of Copper-Transporting ATPases. The American Physiological Society (2007) 87:1011-1046 De Bie, P., Muller, P., et.al. Molecular Pathogenesis of Wilson and Menkes Disease: Correlation of Mutations with Molecular Effects and Disease Phenotypes. Journal of Medical Genetics (2007) 44: 673-688

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