Biochem. J. (2007) 402
(e1–e3) (Printed in Great Britain)
Commentary
Differential regulation of the Menkes and Wilson disease copper transporters by hormones: an integrated model of metal transport in the placenta
Des R. RICHARDSON1 and Yohan SURYO RAHMANTO
Iron Metabolism and Chelation Program, Department of Pathology, Blackburn Building (D06), University of Sydney, Sydney, New South Wales, 2006 Australia
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, identifyferential 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.
Key words: copper transport, Menkes disease, metal trafficking, metal transport, Wilson disease.
1To whom correspondence should be addressed (email d.richardson@med.usyd.edu.au).
Received 11 December 2006/20 December 2006; accepted 3 January 2007
Published on the Internet 12 February 2007, doi:10.1042/BJ20061844
The Biochemical Society, London ©2007
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