title: Cell-surface receptors for gibbon ape leukemia virus and amphotropic murine retrovirus are inducible sodium-dependent phosphate symporters.
abstract: Cell surface receptors for gibbon ape leukemia virus (Glvr-1) and murine amphotropic retrovirus (Ram-1) are distinct but related proteins having multiple membrane-spanning regions. Distant homology with a putative phosphate permease of Neurospora crassa suggested that these receptors might serve transport functions. By expression in Xenopus laevis oocytes and in mammalian cells, we have identified Glvr-1 and Ram-1 as sodium-dependent phosphate symporters. Two-electrode voltage-clamp analysis indicates net cation influx, suggesting that phosphate is transported with excess sodium ions. Phosphate uptake was reduced by > 50% in mouse fibroblasts expressing amphotropic envelope glycoprotein, which binds to Ram-1, indicating that Ram-1 is a major phosphate transporter in these cells. RNA analysis shows wide but distinct tissue distributions, with Glvr-1 expression being highest in bone marrow and Ram-1 in heart. Overexpression of Ram-1 severely repressed Glvr-1 synthesis in fibroblasts, suggesting that transporter expression may be controlled by net phosphate accumulation. Accordingly, depletion of extracellular phosphate increased Ram-1 and Glvr-1 expression 3- to 5-fold. These results suggest simple methods to modulate retroviral receptor expression, with possible applications to human gene therapy.
authors.affiliation: Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland 97201.
authors.forename: M P
authors.initials: MP
authors.lastname: Kavanaugh
authors.forename: D G
authors.initials: DG
authors.lastname: Miller
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Law
authors.forename: S L
authors.initials: SL
authors.lastname: Kozak
authors.forename: D
authors.initials: D
authors.lastname: Kabat
authors.forename: A D
authors.initials: AD
authors.lastname: Miller
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D015870:Gene Expression; D006801:Humans; D017989:Leukemia Virus, Gibbon Ape / Q000378:metabolism*; D009052:Leukemia Virus, Murine / Q000378:metabolism*; D051379:Mice; D009865:Oocytes; D028061:Phosphate Transport Proteins; D028044:Phosphate-Binding Proteins; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins; D012964:Sodium / Q000378:metabolism; D050608:Sodium-Phosphate Cotransporter Proteins; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D027981:Symporters; D014982:Xenopus laevis
chemical_list: D002352:Carrier Proteins; D028061:Phosphate Transport Proteins; D028044:Phosphate-Binding Proteins; D010710:Phosphates; D011991:Receptors, Virus; D011994:Recombinant Proteins; C493586:SLC20A1 protein, human; C493587:Slc20a1 protein, mouse; C493588:Slc20a1 protein, rat; C493565:Slc20a2 protein, mouse; C493566:Slc20a2 protein, rat; D050608:Sodium-Phosphate Cotransporter Proteins; D050611:Sodium-Phosphate Cotransporter Proteins, Type III; D027981:Symporters; C067981:leukemia virus receptor, gibbon ape; D012964:Sodium