Distinct functional roles for the Menkes and Wilson copper translocating P-type ATPases in human placental cells.
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.
Hardman
Belinda
B
Deakin University, Life and Environmental Sciences, Melbourne, Victoria, Australia.
Michalczyk
Agnes
A
Greenough
Mark
M
Camakaris
James
J
Mercer
Jjulian
J
Ackland
Leigh
L
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
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