N-linked glycosylation of the receptor for murine ecotropic retroviruses is altered in virus-infected cells.
Pulse-chase labeling identified incomplete maturation of the cationic amino acid transporter that serves as the receptor for ecotropic retroviruses in infected NIH 3T3 fibroblasts. The molecular basis and functional consequences of this change were studied by expressing viral and receptor proteins in Xenopus oocytes. Expression of the ecotropic, but not polytropic, envelope surface protein, gp70, interfered with N-linked glycosylation of the permissive mouse, but not the nonpermissive, human transporter. Incomplete glycosylation may be a direct consequence of gp70 binding since the glycosylated residues, Asn223 and Asn229, are present in the envelope binding domain. Receptors bearing amino acid substitutions in Asn223 and/or Asn229 that prevent glycosylation function normally in virus infection and amino acid transport. However, gp70 expression sufficient to block binding of 125I-gp70 to the receptor in the plasma membrane decreased receptor-mediated arginine uptake by 50%. Taken together, these findings suggest that newly synthesized gp70 may bind to the receptor in the endoplasmic reticulum and prevent normal glycosylation during their transit to the plasma membrane.
Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, Massachusetts 02115.
J W
JW
Kim
J M
JM
Cunningham
D016475:3T3 Cells; D000818:Animals; D001216:Asparagine / Q000378:metabolism; D001483:Base Sequence; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D004247:DNA; D006031:Glycosylation; D006801:Humans; D007700:Kinetics; D009052:Leukemia Virus, Murine / Q000378:metabolism* / Q000502:physiology; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011991:Receptors, Virus / Q000378:metabolism*; D014779:Virus Replication; D014982:Xenopus laevis
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011991:Receptors, Virus; C070506:ecotropic murine leukemia virus receptor; D001216:Asparagine; D004247:DNA