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

Nature volume 395, pages 288–291 (1998)Cite this article

Abstract

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.

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Figure 1: Transmembrane topology prediction for permease-related putative light chains.
Figure 2: Amino-acid uptake and efflux in Xenopus oocytes expressing h4F2hc and/or the putative light chain ASUR4.
Figure 3: Specificity and Na+ dependence of amino-acid uptake vary when h4F2hc is expressed together with different putative light chains (ASUR4, E16 or SPRM1).
Figure 4: Association of h4F2hc with different light chains: immunoprecipitation of h4F2hc ± light chains (lc) expressed in Xenopus oocytes with anti-h4F2hc antibody followed by SDS–PAGE and fluorography (A, ASUR4; E, E16; S, SPRM1).
Figure 5: Membrane-topology model of a heterodimeric amino-acid transporter of the AmAT family.
Figure 6: Double immunofluorescence detection of h4F2hc and the light-chain SPRM1 in oocyte sections.

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Acknowledgements

We thank L. Kühn and M. Palacin for providing antibody and the h4F2hc cDNA, H.Murer and J. Biber for the Xenopus oocytes, and all four for helpful discussions. We also thank C. Gasser for artwork and L. Dionne, H. J. Kim and L. Kläusli for technical assistance. F.V.'s laboratory is supported by the Swiss NSF and the work in C.B.S.'s laboratory is supported by an NIH grant.

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  1. Luca Mastroberardino and Benjamin Spindler: These authors contributed equally to this work

Authors and Affiliations

  1. Institutes of Physiology and Anatomy, University of Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland

    Luca Mastroberardino, Benjamin Spindler, Rahel Pfeiffer & François Verrey

  2. Institutes of Anatomy, University of Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland

    Jan Loffing

  3. Department of Immunology and Infectious Diseases, Harvard School of Public Health, 665 Huntington Avenue, Boston, 02115, Massachusetts, USA

    Patrick J. Skelly & Charles B. Shoemaker

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  1. Luca Mastroberardino
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Correspondence to François Verrey.

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Mastroberardino, L., Spindler, B., Pfeiffer, R. et al. Amino-acid transport by heterodimers of 4F2hc/CD98 and members of a permease family. Nature 395, 288–291 (1998). https://doi.org/10.1038/26246

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