Human copper transporter Ctr1 is functional in Drosophila, revealing a high degree of conservation between mammals and insects.
Living cells have to carefully control the intracellular concentration of trace metals, especially of copper, which is at the same time essential but owing to its redox activity can also facilitate generation of reactive oxygen species. Mammals have two related copper transporters, Ctr1 and Ctr2, with Ctr1 playing the major role. The fruit fly Drosophila has three family members, termed Ctr1A, Ctr1B, and Ctr1C. Ctr1A is expressed throughout development, and a null mutation causes lethality at an early stage. Ctr1B ensures efficient copper uptake in the intestinal tract, whereas Ctr1C is mainly expressed in male gonads. Ectopic expression of Ctr1 transporters in Drosophila causes toxic effects due to excessive copper uptake. Here, we compare the effects of human Ctr1 (hCtr1) with those of the Drosophila homologs Ctr1A and Ctr1B in two overexpression assays. Whereas the overexpression of Drosophila Ctr1A and Ctr1B results in strong phenotypes, expression of hCtr1 causes only a very mild phenotype, indicating a low copper-import efficiency in the Drosophila system. However, this can be boosted by coexpressing the human copper chaperone CCS. Surprisingly, hCtr1 complements a lethal Ctr1A mutation at least as well as Ctr1A and Ctr1B transgenes. These findings reveal a high level of conservation between the mammalian and insect Ctr1-type copper importers, and they also demonstrate that the Drosophila Ctr1 proteins are functionally interchangeable.
Hua
Haiqing
H
Institute of Molecular Biology, University of Zurich, Switzerland. haiqing.hua@molbio.uzh.ch
Georgiev
Oleg
O
Schaffner
Walter
W
Steiger
Dominik
D
D000818:Animals; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D003300:Copper / Q000378:metabolism / Q000633:toxicity; D000079923:Copper Transporter 1; D004330:Drosophila / Q000187:drug effects / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009154:Mutation
C114678:CCS protein, human; D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D029721:Drosophila Proteins; D018832:Molecular Chaperones; C490079:SLC31A1 protein, human; D003300:Copper