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Copper-induced trafficking of the Cu-ATPase: a key mechanism for copper homeostasis

Mercer, Julian, Barnes, Natalie, Stevenson, Julie, Strausak, Daniel and Llanos, Roxana 2003, Copper-induced trafficking of the Cu-ATPase: a key mechanism for copper homeostasis, BioMetals, vol. 16, no. 1, pp. 175-184, doi: 10.1023/A:1020719016675.

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Title Copper-induced trafficking of the Cu-ATPase: a key mechanism for copper homeostasis
Author(s) Mercer, Julian
Barnes, Natalie
Stevenson, Julie
Strausak, Daniel
Llanos, Roxana
Journal name BioMetals
Volume number 16
Issue number 1
Start page 175
End page 184
Publisher Kluwer Academic Publishers
Place of publication Amsterdam, The Netherlands
Publication date 2003-03
ISSN 0966-0844
1572-8773
Keyword(s) copper transport
Cu ATPase
Menkes disease
Wilson disease
Summary The Menkes protein (MNK) and Wilson protein (WND) are transmembrane, CPX-type Cu-ATPases with six metal binding sites (MBSs) in the N-terminal region containing the motif GMXCXXC. In cells cultured in low copper concentration MNK and WND localize to the transGolgi network but in high copper relocalize either to the plasma membrane (MNK) or a vesicular compartment (WND). In this paper we investigate the role of the MBSs in Cu-transport and trafficking. The copper transport activity of MBS mutants of MNK was determined by their ability to complement a strain of Saccharomyces cerevisiae deficient in CCC2 (Deltaccc2), the yeast MNK/WND homologue. Mutants (CXXC to SXXS) of MBS1, MBS6, and MBSs1-3 were able to complement Deltaccc2 while mutants of MBS4-6, MBS5-6 and all six MBS inactivated the protein. Each of the inactive mutants also failed to display Cu-induced trafficking suggesting a correlation between trafficking and transport activity. A similar correlation was found with mutants of MNK in which various MBSs were deleted, but two constructs with deletion of MBS5-6 were unable to traffic despite retaining 25% of copper transport activity. Chimeras in which the N-terminal MBSs of MNK were replaced with the corresponding MBSs of WND were used to investigate the region of the molecules that is responsible for the difference in Cu-trafficking of MNK and WND. The chimera which included the complete WND N-terminus localized to a vesicular compartment, similar to WND in elevated copper. Deletions of various MBSs of the WND N-terminus in the chimera indicate that a targeting signal in the region of MBS6 directs either WND/MNK or WND to a vesicular compartment of the cell.
Notes Published on line: September 2002
Language eng
DOI 10.1023/A:1020719016675
Field of Research 060199 Biochemistry and Cell Biology not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2003, Kluwer Academic Publishers
Persistent URL http://hdl.handle.net/10536/DRO/DU:30002077

Document type: Journal Article
Collection: School of Biological and Chemical Sciences
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