Cell-Surface Receptors for Gibbon Ape Leukemia Virus and Amphotropic Murine Retrovirus are Inducible Sodium-Dependent Phosphate Symporters

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 15; pp. 7071 - 7075
• Main Authors: Kavanaugh, Michael P., Miller, Daniel G., Zhang, Weibin, Law, Wendy, Kozak, Susan L., Kabat, David, Miller, A. Dusty
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 19-07-1994; National Acad Sciences; National Academy of Sciences
• Subjects: 3T3 Cells; AIDS/HIV; Animals; Biological Transport; Bone marrow cells; Carrier Proteins - metabolism; Cell Line; Cell lines; Cells; Cellular biology; CHO cells; Fibroblasts; Gene Expression; Humans; Leukemia; Leukemia Virus, Gibbon Ape - metabolism; Leukemia Virus, Murine - metabolism; Mice; Monkeys & apes; murine leukemia virus; NIH 3T3 cells; Oocytes; Phosphate Transport Proteins; Phosphate-Binding Proteins; Phosphates; Phosphates - metabolism; Rats; Receptors; Receptors, Virus - genetics; Receptors, Virus - metabolism; Recombinant Proteins; RNA; Sodium - metabolism; Sodium-Phosphate Cotransporter Proteins; Sodium-Phosphate Cotransporter Proteins, Type III; Symporters; Xenopus laevis
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.15.7071

Cell surface receptors for gibbon ape leukemia virus (Glvr-1) and murine amphotropic retrovirus (Ram-1) are distinct but related proteins having multiple membranespanning 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.