title: Metal transporters that contribute copper to metallochaperones in Saccharomyces cerevisiae.
abstract: Copper metallochaperones represent a new family of soluble, low-molecular-weight proteins that function to deliver copper to specific sites within a cell. How the metallochaperones acquire their copper, however, is not known. In this study, we have conducted a survey of known metal ion transporters in bakers' yeast, Saccharomyces cerevisiae, to identify those that contribute copper to pathways involving the metallochaperones Atxlp and Lys7p. The results indicatethat, in addition to the well known Ctr1p and Ctr3p high-affinity copper transporters, the metallochaperones can acquire their copper through pathways involving the relatively non-specific divalent metal ion transporter Fet4p and the putative low-affinitycopper transporter Ctr2p. We have examined the localization of Ctr2p using an epitope tagged version of the protein and find that Ctr2p does not localize to the cell surface but may operate at the level of the vacuole to mobilize intracellular copper. Inaddition to Ctrlp, Ctr2p, Ctr3p and Fet4p, other metal transport systems can act as upstream donors of copper for the metallochaperones when copper availability in the medium is increased. Although the nature of these auxiliary systems is unknown, they do not appear to involve the yeast members of the Nramp family of divalent transporters, or uptake mechanisms that involve endocytosis. Since vastly different metal transporters located at either the cell surface or intracellular sites can all contribute copper to metallochaperones, it is unlikely that the metallochaperones directly interact with the metal transporters to obtain the metal.
authors.affiliation: Department of Biochemistry, Johns Hopkins University School of Public Health, Baltimore, MD 21205, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Portnoy
authors.forename: P J
authors.initials: PJ
authors.lastname: Schmidt
authors.forename: R S
authors.initials: RS
authors.lastname: Rogers
authors.forename: V C
authors.initials: VC
authors.lastname: Culotta
mesh_terms: D017920:Antiporters / Q000235:genetics* / Q000378:metabolism; D029681:Arabidopsis Proteins; D027682:Cation Transport Proteins; D003300:Copper / Q000378:metabolism; D000079923:Copper Transporter 1; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D000080083:SLC31 Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D017920:Antiporters; D029681:Arabidopsis Proteins; C433183:CCH protein, Arabidopsis; C490078:CTR1 protein, S cerevisiae; C100982:CTR3 protein, S cerevisiae; D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D008565:Membrane Proteins; D018832:Molecular Chaperones; D000080083:SLC31 Proteins; D029701:Saccharomyces cerevisiae Proteins; D003300:Copper