Conservation of copper-transporting P(IB)-type ATPase function

Southon, Adam, Palstra, Nickless, Veldhuis, Nicholas, Gaeth, Ann, Robin, Charles, Burke, Richard and Camakaris, James (2010) Conservation of copper-transporting P(IB)-type ATPase function. Biometals, 23 4: 681-694. doi:10.1007/s10534-010-9332-2

Author Southon, Adam
Palstra, Nickless
Veldhuis, Nicholas
Gaeth, Ann
Robin, Charles
Burke, Richard
Camakaris, James
Title Conservation of copper-transporting P(IB)-type ATPase function
Journal name Biometals   Check publisher's open access policy
ISSN 0966-0844
Publication date 2010-08
Sub-type Article (original research)
DOI 10.1007/s10534-010-9332-2
Volume 23
Issue 4
Start page 681
End page 694
Total pages 14
Place of publication Dordrecht, Netherlands
Publisher Springer Netherlands
Language eng
Formatted abstract
Copper-transporting P(IB)-type ATPases are highly conserved, and while unicellular eukaryotes and invertebrates have only one, a gene duplication has occurred during vertebrate evolution. Copper-induced trafficking of mammalian ATP7A and ATP7B from the trans-Golgi Network towards the plasma membrane is critical for their role in copper homeostasis. In polarized epithelial cells ATP7A and ATP7B traffic towards the basolateral and apical membranes respectively. We examined the localization and function of DmATP7, the single Drosophila melanogaster orthologue, in cultured D. melanogaster and mammalian cells to explore the conservation of P(IB)-type ATPase function. Comparative genomic analysis demonstrated motifs involved in basolateral targeting and retention of ATP7A were conserved in DmATP7, whereas ATP7B targeting motifs were not. DmATP7 expression was able to correct the copper hyper-accumulation phenotype of cultured fibroblasts from a Menkes disease patient expressing a null ATP7A allele. DmATP7 was able to transport copper to the cupro-enzyme tyrosinase and under elevated copper conditions DmATP7 was able to traffic towards the plasma membrane and efflux copper, essentially phenocopying ATP7A. When expressed in polarized Madin-Darby Canine Kidney cells, DmATP7 translocated towards the basolateral membrane when exposed to elevated copper, similar to ATP7A. These results demonstrate DmATP7 is able to functionally compensate for the absence of ATP7A, with important trafficking motifs conserved in these distantly related orthologues.
Keyword Menkes
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
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Created: Wed, 19 Oct 2011, 09:47:32 EST by Nick Palstra on behalf of Queensland Brain Institute