This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Peter, C.
Right arrow Articles by Labbé, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Peter, C.
Right arrow Articles by Labbé, S.

 Previous Article  |  Next Article 

Eukaryotic Cell, October 2008, p. 1781-1794, Vol. 7, No. 10
1535-9778/08/$08.00+0     doi:10.1128/EC.00230-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Copper Distributed by Atx1 Is Available to Copper Amine Oxidase 1 in Schizosaccharomyces pombe{triangledown}

Chardeen Peter, Julie Laliberté, Jude Beaudoin, and Simon Labbé*

Département de Biochimie, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada

Received 14 July 2008/ Accepted 18 August 2008

Copper amine oxidases (CAOs) have been proposed to be involved in the metabolism of xenobiotic and biogenic amines. The requirement for copper is absolute for their activity. In the fission yeast Schizosaccharomyces pombe, cao1+ and cao2+ genes are predicted to encode members of the CAO family. While both genes are expressed in wild-type cells, we determined that the expression of only cao1+ but not cao2+ results in the production of an active enzyme. Site-directed mutagenesis identified three histidine residues within the C-terminal region of Cao1 that are necessary for amine oxidase activity. By use of a cao1+-GFP allele that retained wild-type function, Cao1-GFP was localized in the cytosol (GFP is green fluorescent protein). Under copper-limiting conditions, disruption of ctr4+, ctr5+, and cuf1+ produced a defect in amine oxidase activity, indicating that a functionally active Cao1 requires Ctr4/5-mediated copper transport and the transcription factor Cuf1. Likewise, atx1 null cells exhibited substantially decreased levels of amine oxidase activity. In contrast, deletion of ccc2, cox17, and pccs had no significant effect on Cao1 activity. Residual amine oxidase activity in cells lacking atx1+ can be restored to normal levels by returning an atx1+ allele, underscoring the critical importance of the presence of Atx1 in cells. Using two-hybrid analysis, we demonstrated that Cao1 physically interacts with Atx1 and that this association is comparable to that of Atx1 with the N-terminal region of Ccc2. Collectively, these results describe the first example of the ability of Atx1 to act as a copper carrier for a molecule other than Ccc2 and its critical role in delivering copper to Cao1.

* Corresponding author. Mailing address: Département de Biochimie, Faculté de médecine, Université de Sherbrooke, 3001 12e Ave. Nord, Sherbrooke, Québec J1H 5N4, Canada. Phone: (819) 820-6868, ext. 15460. Fax: (819) 564-5340. E-mail: Simon.Labbe{at}USherbrooke.ca

{triangledown} Published ahead of print on 22 August 2008.

Eukaryotic Cell, October 2008, p. 1781-1794, Vol. 7, No. 10
1535-9778/08/$08.00+0     doi:10.1128/EC.00230-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»