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 exchangers. 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 sodium. The molecular nature of these transporters remains unknown, although expression of the human cell-surface glycoprotein 4F2 heavy chain (h4F2hc; CD98 in the mouse) is known to induce low levels of L- and/or y(+)L-type transport. 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 (M(r) 40K). Here we identify the permease-related protein E16 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.
Mastroberardino
L
L
Institute of Physiology, University of Zürich, Switzerland.
Spindler
B
B
Pfeiffer
R
R
Skelly
P J
PJ
Loffing
J
J
Shoemaker
C B
CB
Verrey
F
F
D026905:Amino Acid Transport Systems; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D019281:Dimerization; D027261:Fusion Regulatory Protein-1; D015801:Helminth Proteins / Q000378:metabolism; D006801:Humans; D027283:Large Neutral Amino Acid-Transporter 1; D007930:Leucine / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000378:metabolism; D012550:Schistosoma mansoni; D012964:Sodium / Q000378:metabolism; D014981:Xenopus
D026905:Amino Acid Transport Systems; D000596:Amino Acids; D015703:Antigens, CD; D002352:Carrier Proteins; D027261:Fusion Regulatory Protein-1; D015801:Helminth Proteins; D027283:Large Neutral Amino Acid-Transporter 1; D008565:Membrane Proteins; D011994:Recombinant Proteins; D012964:Sodium; D007930:Leucine