High affinity copper transport in yeast

Kacchawmyces ccrevisiae has proven to be an ideal model organism to study trace metal metabolism in eukaryotes. Here we describe a protein (Ctr3p) that restores; Cu and Fe uptake, growth on non-fermentable carbon sources, and Cu, Zn Superoxide d ismutase activity to strains lacking the copper transport protein, Ctrlp. CTR3 gene expression is inactivated in the majority of yeast strains by a transposable element within the CTR3 gene promoter. In yeast cells expressing both the CTR2 and CTR3 genes the inactivation of both genes is required to generate a Cu-deficient phonotype. In these cells CTR3 mRNA and Ctr3p protein levels are repressed by Cu. CtrSp is a 241 amino acid membrane protein with eleven cysteine residues that is located in the endoplasmic reticulum and secretory compartments of the cell. The functional independence of Ctrlp and Ctr3p suggest that yeast have two high affinity Cu uptake pathways. Funding: NIH fellowship F32 GM 15662-01 to S.A.B.K., NIH grants UP1 GM46787 to D.|.K. and ROI CM41840 to D.J.T.