title: Essential roles in development and pigmentation for the Drosophila copper transporter DmATP7.
abstract: 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.
authors.affiliation: Department of Genetics, The University of Melbourne, Parkville VIC 3010, Australia.
authors.forename: Melanie
authors.initials: M
authors.lastname: Norgate
authors.forename: Esther
authors.initials: E
authors.lastname: Lee
authors.forename: Adam
authors.initials: A
authors.lastname: Southon
authors.forename: Ashley
authors.initials: A
authors.lastname: Farlow
authors.forename: Philip
authors.initials: P
authors.lastname: Batterham
authors.forename: James
authors.initials: J
authors.lastname: Camakaris
authors.forename: Richard
authors.initials: R
authors.lastname: Burke
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal / Q000235:genetics; D006197:Hair / Q000254:growth & development / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D009035:Mothers; D009154:Mutation / Q000235:genetics; D010858:Pigmentation / Q000502:physiology*; D013997:Time Factors; D019076:Transgenes / Q000235:genetics
chemical_list: C497836:ATP7 protein, Drosophila; D027682:Cation Transport Proteins; D003300:Copper; D000073840:Copper-Transporting ATPases