Cell-surface receptor for ecotropic murine retroviruses is a basic amino-acid transporter.
The complementary DNA sequence encoding the cell-surface receptor for ecotropic host-range murine retroviruses (ecoR) shows that it contains 622 amino acids and 14 hydrophobic potentially membrane-spanning sequences. Because this receptor occurs on many or all murine cells and is probably essential for viability of cultured fibroblasts, its normal function might be to transport an essential metabolite. We expressed ecoR in Xenopus laevis oocytes by injecting RNA transcribed from the cloned cDNA. These oocytes specifically bound the gp70 envelope glycoprotein from an ecotropic murine leukaemia virus. An inward current was recorded electrophysiologically when a mixture of amino-acids was applied: this resulted from a stereoselective, saturable uptake of lysine, arginine and ornithine; it was independent of sodium and not substantially altered by gp70. Cysteine and homoserine were also taken up, but sodium was necessary for their transport. These properties of ecoR correspond to those of the y+ amino-acid transporter. Our results demonstrate the subversion of a ubiquitous cell membrane protein, in this case a basic amino acid transporter, for use as a retroviral receptor.
Wang
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Department of Biochemistry, Oregon Health Sciences University, Portland 97201.
Kavanaugh
M P
MP
North
R A
RA
Kabat
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D
D000818:Animals; D001120:Arginine / Q000378:metabolism; D001692:Biological Transport; D002412:Cations; D003001:Cloning, Molecular; D004553:Electric Conductivity; D066298:In Vitro Techniques; D007700:Kinetics; D008239:Lysine / Q000378:metabolism; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008979:Moloney murine leukemia virus; D009952:Ornithine / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins / Q000378:metabolism; D014982:Xenopus laevis
D002412:Cations; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D011991:Receptors, Virus; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C070506:ecotropic murine leukemia virus receptor; D001120:Arginine; D009952:Ornithine; D008239:Lysine