4F2 (CD98) heavy chain is associated covalently with an amino acid transporter and controls intracellular trafficking and membrane topology of 4F2 heterodimer

4F2, also termed CD98, is an integral membrane protein consisting of a heav y chain linked to a light chain by disulfide bond. We have generated a mono clonal antibody to the mouse 4F2 light chain and cloned the cDNA It encodes a mouse counterpart of rat L-type amino acid transporter-1, and induces sy stem L amino acid transport in Xenopus oocytes in the presence of 4F2 heavy chain. Transfection studies in mammalian cells have indicated that the 4F2 heavy chain is expressed on the plasma membrane on its own, whereas the 4F 2 light chain can be transported to the surface only in the presence of 4F2 heavy chain. 4F2 heavy chain is expressed diffusely on the surface of fibr oblastic L cells, whereas it is localized selectively to the cell-cell adhe sion sites in L cells expressing cadherins, These results indicate that the 4F2 heavy chain is associated covalently with an amino acid transporter an d controls the cell surface expression as well as the membrane topology of the 4F2 heterodimer. Although 4F2 heavy and light chains are expressed coor dinately in most tissues, the light chain is barely detected by the antibod y in kidney and intestine, despite the presence of heavy chain in a complex form. The results predict the presence of multiple 4F2 light chains.