title: Malvolio is a copper transporter in Drosophila melanogaster.
abstract: Divalent metal ion transporter 1 (DMT1; also known as SLC11A2) can transport several metals including Fe and Cu in mammalian systems. We set out to determine whether Malvolio (Mvl), the Drosophila melanogaster orthologue of DMT1, can also transport Cu. Overexpression of Mvl caused Cu accumulation in Drosophila S2 cultured cells and conversely dsRNAi knockdown of endogenous Mvl reduced cellular Cu levels. Cell viability under Cu limiting conditions was reduced following dsRNAi knockdown. A homozygous viable Mvl loss-of-function mutant (Mvl(97f)) was sensitive to excess Cu and female Mvl(97f) flies were also sensitive to Cu limitation. An MtnA-EYFP reporter was used as a proxy measure of Cu distribution within Mvl(97f/+) larvae. Under basal conditions Cu levels were reduced in the anterior midgut and proventriculus relative to control larvae. These results demonstrate Mvl is a functional Cu transporter and that despite partial functional redundancy with the Ctr1 proteins, Cu uptake through this pathway is necessary for optimal viability at the cellular and organismal levels.
authors.affiliation: Department of Genetics, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Adam
authors.initials: A
authors.lastname: Southon
authors.forename: Ashley
authors.initials: A
authors.lastname: Farlow
authors.forename: Melanie
authors.initials: M
authors.lastname: Norgate
authors.forename: Richard
authors.initials: R
authors.lastname: Burke
authors.forename: James
authors.initials: J
authors.lastname: Camakaris
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D003300:Copper / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D016623:Ion Pumps / Q000235:genetics / Q000378:metabolism*; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010858:Pigmentation / Q000235:genetics / Q000502:physiology; D034622:RNA Interference
chemical_list: D017931:DNA Primers; D029721:Drosophila Proteins; D016623:Ion Pumps; D008565:Membrane Proteins; C094756:mvl protein, Drosophila; D003300:Copper