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MBC in Press, published online ahead of print October 26, 2005
Mol. Biol. Cell 10.1091/mbc.E05-06-0492

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Submitted on June 6, 2005
Revised on September 29, 2005
Accepted on October 17, 2005

Essential Roles in Development and Pigmentation for the Drosophila Copper Transporter DmATP7

Melanie Norgate,*{dagger} Esther Lee,*{dagger} Adam Southon,* Ashley Farlow,*{dagger} Philip Batterham,*{dagger} James Camakaris,* and Richard Burke*

*Department of Genetics and {dagger}Centre for Environmental Stress and Adaptation Research (CESAR), The University of Melbourne, Parkville VIC 3010, Australia

Monitoring Editor: Jeffrey Brodsky

Defects in the mammalian Menkes and Wilson copper transporting P-type ATPases cause severe copper homeostasis disease phenotypes in humans. Here we find that DmATP7, the sole Drosophila orthologue of the Menkes and Wilson genes, is vital for uptake of copper in vivo. Analysis of a DmATP7 loss-of-function allele shows that DmATP7 is essential in embryogenesis, early larval development and adult pigmentation, and is probably required for copper uptake from the diet. These phenotypes are analogous to those caused by mutation in the mouse and human Menkes genes, suggesting that like Menkes, DmATP7 plays at least two roles at the cellular level, delivering copper to cuproenzymes required for pigmentation and neuronal function, and removing excess cellular copper via facilitated efflux. DmATP7 displays a dynamic and unexpected expression pattern in the developing embryo, implying novel functions for this copper pump and the lethality observed in DmATP7 mutant flies is the earliest seen for any copper homeostasis gene.

Address correspondence to: James Camakaris (j.camakaris{at}unimelb.edu.au)




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