Differential regulation of the Menkes and Wilson disease copper transporters by hormones: an integrated model of metal transport in the placenta.

Des R. Richardson, Yohan Suryo Rahmanto

Research output: Contribution to journalComment/debate

Abstract

Copper (Cu) plays a critical role in the developing foetus, but virtually nothing is known concerning the regulation of its uptake and metabolism in the placenta. In this issue of the Biochemical Journal, Hardman and colleagues, using a model of placental trophoblasts in culture, identify differential hormonal regulation of two copper-transporting ATPases; namely, those responsible for Menkes disease (ATP7A; MNK) and Wilson disease (ATP7B; WND). Insulin and oestrogen, which are essential during gestation, up-regulate MNK and this leads to trafficking of the MNK protein from the Golgi to the basolateral membrane, resulting in increased Cu efflux. At the same time, insulin decreased WND levels, and this leads to intracellular sequestration of the protein to a perinuclear region that reduces apical Cu release. As such, this results in a concerted flux of Cu from the basolateral surface of the trophoblast that would potentially be used by the developing foetus. An integrated model of vectorized Cu transport is proposed, which involves co-ordinated expression of transporters, organelle interactions and probable protein-protein interactions. The findings have wider implications for considering general models of intracellular metal transport.

Original languageEnglish (US)
JournalThe Biochemical journal
Volume402
Issue number2
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

Fingerprint

Menkes Kinky Hair Syndrome
Hepatolenticular Degeneration
Placenta
Copper
Metals
Trophoblasts
Hormones
Fetus
Insulin
Proteins
Protein Transport
Organelles
Estrogens
Up-Regulation
Metabolism
Pregnancy
Membranes
Fluxes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Differential regulation of the Menkes and Wilson disease copper transporters by hormones : an integrated model of metal transport in the placenta. / Richardson, Des R.; Suryo Rahmanto, Yohan.

In: The Biochemical journal, Vol. 402, No. 2, 01.03.2007.

Research output: Contribution to journalComment/debate

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