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

J Biol Chem. 1999 Jan 29;274(5):3009-16. doi: 10.1074/jbc.274.5.3009.


4F2, also termed CD98, is an integral membrane protein consisting of a heavy chain linked to a light chain by disulfide bond. We have generated a monoclonal 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 system 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 4F2 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 fibroblastic L cells, whereas it is localized selectively to the cell-cell adhesion sites in L cells expressing cadherins. These results indicate that the 4F2 heavy chain is associated covalently with an amino acid transporter and controls the cell surface expression as well as the membrane topology of the 4F2 heterodimer. Although 4F2 heavy and light chains are expressed coordinately in most tissues, the light chain is barely detected by the antibody in kidney and intestine, despite the presence of heavy chain in a complex form. The results predict the presence of multiple 4F2 light chains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems
  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antigens, CD / metabolism*
  • Antigens, Surface / metabolism*
  • Biological Transport
  • Carrier Proteins / metabolism*
  • Cell Membrane / metabolism
  • Cricetinae
  • Dimerization
  • Disulfides / metabolism
  • Fusion Regulatory Protein-1
  • Intestinal Mucosa / metabolism
  • Kidney / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Rats
  • Xenopus


  • Amino Acid Transport Systems
  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Surface
  • Carrier Proteins
  • Disulfides
  • Fusion Regulatory Protein-1

Associated data

  • GENBANK/AB017189