title: Distinct functional roles for the Menkes and Wilson copper translocating P-type ATPases in human placental cells.
abstract: OBJECTIVE
  The copper transporting ATPases, Menkes (ATP7A; MNK) and Wilson (ATP7B; WND) are essential for normal copper transport in the human body. The placenta is the key organ in copper supply to the fetus during pregnancy and it is one of the few organs in the body to express both of the ATPases. The placenta therefore provides a unique opportunity to elucidate the specific roles of these transporters within the one cell type.
  
  
  RESULTS
  Using polarized placental Jeg-3 cells, siRNA technology and radio-labelled 64Cu transport assays, MNK and WND were shown to have distinct roles in the vectorial transport of copper. MNK transported copper from the cell via the basolateral membrane and in contrast, WND transported copper from the apical membrane. Inactivation of MNK resulted in decreased activity of two important cuproenzymes, lysyl oxidase and Cu/Zn-superoxide dismutase.
  
  
  CONCLUSIONS
  Overall, these results provide definitive evidence for distinct roles of MNK and WND in the human placenta, and are consistent with a role for MNK in the transport of copper into the fetal circulation, and through delivery of copper to placental cuproenzymes, whilst WND contributes to the maintenance of placental copper homeostasis by transporting copper to the maternal circulation.
authors.affiliation: Deakin University, Life and Environmental Sciences, Melbourne, Victoria, Australia.
authors.forename: Belinda
authors.initials: B
authors.lastname: Hardman
authors.forename: Agnes
authors.initials: A
authors.lastname: Michalczyk
authors.forename: Mark
authors.initials: M
authors.lastname: Greenough
authors.forename: James
authors.initials: J
authors.lastname: Camakaris
authors.forename: Jjulian
authors.initials: J
authors.lastname: Mercer
authors.forename: Leigh
authors.initials: L
authors.lastname: Ackland
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D010920:Placenta / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D011247:Pregnancy; D008249:Protein-Lysine 6-Oxidase / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014162:Transfection
chemical_list: D027682:Cation Transport Proteins; D034741:RNA, Small Interfering; D003300:Copper; D013482:Superoxide Dismutase; D008249:Protein-Lysine 6-Oxidase; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases