Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family

Amino-acid transport across cellular plasma membranes depends on several parallel-functioning (co-)transporters and exchangers1. The widespread transport system L accounts for a sodium-independent exchange of large, neutral amino acids, whereas the system y+L exchanges positively charged amino acids and/or neutral amino acids together with sodium2,3. The molecular nature of these transporters remains unknown, although expression of the human cell-surface glycoprotein 4F2 heavy chain (h4F2hc; CD98 in the mouse)4,5 is known to induce low levels of L- and/or y+L-type transport6,7,8,9. This glycoprotein is found in activated lymphocytes, together with an uncharacterized, disulphide-linked lipophilic light chain with an apparent relative molecular mass of 40,000 (Mr 40K)10,11. Here we identify the permease-related protein E16 (ref. 12) as the first light chain of h4F2hc and show that the resulting heterodimeric complex mediates L-type amino-acid transport. The homologous protein from Schistosoma mansoni, SPRM1, also associates covalently with coexpressed h4F2hc glycoprotein, although it induces amino-acid transport of different substrate specificity. The coexpression of h4F2hc is required for surface expression of these permease-related light chains, which belong to a new family of amino-acid transporters that form heterodimers with cell-surface glycoproteins.