[Relations between CTR1 gene activity and copper status in different rat organs]

Abstract

CTR1 gene (SLC31A1 according to Entrez data base) product is the main candidate for the role of eukaryotic copper importer, whose tissue-specific function is still unclear. In this research steady state CTR1-mRNA level was measured with semiquantitative RT-PCR analysis and compared with copper status in rat organs, in which copper metabolism is changed during development (liver, cerebellum, choroid plexus and mammary gland). It has been shown that CTR1 gene activity correlates with the rate of both intracellular and extracellular copper-containing enzymes formation. In mesenchymal origin cells of newborns the CTR1 gene activity decreases when high copper concentrations in cell nucleus is reached. According to phylogenetic analysis CTR1 has the most conservative transmembrane domains 2 and 3 (TMD), containing 7 amino acid residues able to coordinate copper atom. A model of cuprophylic channel has been proposed, which is formed by TMD2 and TMD3 in homotrimeric CTR1 complex. In this model copper is transported through the channel to cytosolic C-terminal motif His-Cys-His, which ability to coordinate Cu(I) was assessed by molecular modeling (MM+, ZINDO/1). Theoretical possibility of copper transfer from His-Cys-His CTR1 C-terminal motif to cytosolic Cys-X-X-Cys Cu(I) chaperon sites has been shown. The role of CTR1 in copper metabolism as copper donor and acceptor is discussed.