Identification and characterisation of human xCT that co-expresses, with 4F2 heavy chain, the amino acid transport activity system x(c)(-)

We have identified a new human complementary deoxyribonucleic acid (cDNA), for the x(c)(-) amino acid transporter (HGMW-approved name SLC7A11; also kn own as human xCT), that, when co-expressed with the heavy chain of surface antigen 4F2 (4F2hc, also termed CD98), but not with rBAT, (related to the b (o,+) amino acid transporter), induces system x(c)(-) transport activity in Xenopus oocytes. Human xCT is the seventh human member of the family of am ino acid transporters that are subunits of 4F2hc or rBAT and, inview of its amino acid sequence identity (89%) with mouse xCT, is most probably the hu man orthologue thereof. The amino acid transport activity induced by the co -expression of human 4F2hc and xCT in Xenopus oocytes was sodium independen t and specific for L-cystine, L-glutamate and L-aspartate. This activity al so functioned in an exchange mode (e,g. cystine/glutamate) with a substrate stoichiometry of 1:1. Expression of human xCT alone in oocytes did not ind uce amino acid transport activity and the expressed xCT protein was localis ed intracellularly. When human xCT was co-expressed with 4F2hc, the former localised to the oocyte plasma membrane. Tissue-expression studies showed t hat human SLC7A11 mRNA is expressed mainly in the brain, but also in pancre as and in cultured cell lines. The transport characteristics of human xCT a nd the distribution of its tissue expression strongly suggest that it corre sponds to the human amino acid transporter system x(c)(- .) Oocytes.