Cell Physiology

Function and structure of heterodimeric amino acid transporters

Carsten A. Wagner, Florian Lang, Stefan Bröer


Heterodimeric amino acid transporters are comprised of two subunits, a polytopic membrane protein (light chain) and an associated type II membrane protein (heavy chain). The heavy chain rbAT (related to b0,+ amino acid transporter) associates with the light chain b0,+AT (b0,+ amino acid transporter) to form the amino acid transport system b0,+, whereas the homologous heavy chain 4F2hc interacts with several light chains to form system L (with LAT1 and LAT2), system y+L (with y+LAT1 and y+LAT2), system x c (with xAT), or system asc (with asc1). The association of light chains with the two heavy chains is not unambiguous. rbAT may interact with LAT2 and y+LAT1 and vice versa; 4F2hc may interact with b0,+AT when overexpressed. 4F2hc is necessary for trafficking of the light chain to the plasma membrane, whereas the light chains are thought to determine the transport characteristics of the respective heterodimer. In contrast to 4F2hc, mutations in rbAT suggest that rbAT itself takes part in the transport besides serving for the trafficking of the light chain to the cell surface. Heavy and light subunits are linked together by a disulfide bridge. The disulfide bridge, however, is not necessary for the trafficking of rbAT or 4F2 heterodimers to the membrane or for the functioning of the transporter. However, there is experimental evidence that the disulfide bridge in the 4F2hc/LAT1 heterodimer plays a role in the regulation of a cation channel. These results highlight complex interactions between the different subunits of heterodimeric amino acid transporters and suggest that despite high grades of homology, the interactions between rbAT and 4F2hc and their respective partners may be different.

  • heavy and light chains
  • disulfide bridge
  • cystinuria
  • lysinuric protein intolerance


  • This work was supported by grants from the European Community (to F. Lang), the Deutsche Forschungsgemeinschaft (to S. Bröer and F. Lang), and the Federal Ministry of Education, Science, Education, Research, and Technology (01KS9602, IZKF Tübingen to F. Lang and C. A. Wagner).

  • C. A. Wagner is a Feodor-Lynen fellow of the Alexander von Humboldt Foundation, Germany.

  • Address for reprint requests and other correspondence: C. A. Wagner, Dept. of Cellular and Molecular Physiology, School of Medicine, Yale Univ., 333 Cedar St., New Haven, CT 06520 (E-mail:wagnerca{at}hotmail.com).

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