title: The Drosophila copper transporter Ctr1C functions in male fertility.
abstract: Living organisms have evolved intricate systems to harvest trace elements from the environment, to control their intracellular levels, and to ensure adequate delivery to the various organs and cellular compartments. Copper is one of these trace elements. It is at the same time essential for life but also highly toxic, not least because it facilitates the generation of reactive oxygen species. In mammals, copper uptake in the intestine and copper delivery into other organs are mediated by the copper importer Ctr1. Drosophila has three Ctr1 homologs: Ctr1A, Ctr1B, and Ctr1C. Earlier work has shown that Ctr1A is an essential gene that is ubiquitously expressed throughout development, whereas Ctr1B is responsible for efficient copper uptake in the intestine. Here, we characterize the function of Ctr1C and show that it functions as a copper importer in the male germline, specifically in maturing spermatocytes and mature sperm. We further demonstrate that loss of Ctr1C in a Ctr1B mutant background results in progressive loss of male fertility that can be rescued by copper supplementation to the food. These findings hint at a link between copper and male fertility, which might also explain the high Ctr1 expression in mature mammalian spermatozoa. In both mammals and Drosophila, the X chromosome is known to be inactivated in the male germline. In accordance with such a scenario, we provide evidence that in Drosophila, the autosomal Ctr1C gene originated as a retrogene copy of the X-linked Ctr1A, thus maintaining copper delivery during male spermatogenesis.
authors.affiliation: Institute of Molecular Life Sciences, University of Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Dominik
authors.initials: D
authors.lastname: Steiger
authors.forename: Michael
authors.initials: M
authors.lastname: Fetchko
authors.forename: Alla
authors.initials: A
authors.lastname: Vardanyan
authors.forename: Lilit
authors.initials: L
authors.lastname: Atanesyan
authors.forename: Kurt
authors.initials: K
authors.lastname: Steiner
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Turski
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Thiele
authors.forename: Oleg
authors.initials: O
authors.lastname: Georgiev
authors.forename: Walter
authors.initials: W
authors.lastname: Schaffner
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000235:genetics / Q000494:pharmacology*; D003300:Copper / Q000378:metabolism*; D000079922:Copper Transport Proteins; D003433:Crosses, Genetic; D029721:Drosophila Proteins / Q000235:genetics / Q000494:pharmacology*; D004331:Drosophila melanogaster; D005260:Female; D005298:Fertility / Q000235:genetics*; D005786:Gene Expression Regulation; D008297:Male; D008954:Models, Biological; D012098:Reproduction; D013090:Spermatocytes / Q000378:metabolism; D013094:Spermatozoa / Q000378:metabolism; D049951:X Chromosome Inactivation
chemical_list: D027682:Cation Transport Proteins; D000079922:Copper Transport Proteins; C550077:Ctr1C protein, Drosophila; D029721:Drosophila Proteins; D003300:Copper