Function of Copper Transporters By Stefano Pineda Overview

Function of Copper Transporters By: Stefano Pineda

Overview • • Copper Importers – Ctr 1 – Ctr 2 Copper Exporters – ADP 7 A – ADP 7 B

Distribution of copper

Copper Uptake Ctr 1 h. Ctr 1 Integral plasma protein •

Where is CTR 1 Expressed? Kuo Y et al. PNAS 2001; 98: 6836 -6841

CTR 1's Role in Development

Intracellular Copper Distribution

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 ATP 7 A & ATP 7 B dual function based off intracellular Cu concentration.

Copper Export: Cu-ATPases

Dual Function of Cu-ATPases

ATP 7 A 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

ATP 7 B Liver central organ in copper homeostasis Export of excess copper out of the body Hepatic trans-Golgi network contain ATP 7 B Receive copper from Atox 1 transport it into lumen of the TGN Incorporated into copper-dependent ferroxidase ceruloplasmin, most abundant copper containing protein in blood Copper secretion into bile

ATP 7 A and ATP 7 B Copper Distribution

In Conclusion CTR 1, 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

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