1. Function of Copper Transporters
By: Stefano Pineda

2. Overview
Copper Importers
Ctr1
Ctr2
Copper Exporters
ADP7A
ADP7B

3. Distribution of copper

4. Integral membrane proteins with 3 transmembrane domains that form a homotrimeric pore for import of Cu+ 4
Copper Uptake Ctr1
hCtr1
Integral plasma protein

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

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
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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:
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: