CELL-SURFACE RECEPTORS FOR GIBBON APE LEUKEMIA-VIRUS AND AMPHOTROPIC MURINE RETROVIRUS ARE INDUCIBLE SODIUM-DEPENDENT PHOSPHATE SYMPORTERS

Cell surface receptors for gibbon ape leukemia virus (Glvr-1) and muri ne amphotropic retrovirus (Ram-1) are distinct but related proteins ha ving multiple membrane-spanning regions. Distant homology with a putat ive phosphate permease of Neurospora crassa suggested that these recep tors 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 an alysis indicates net cation influx, suggesting that phosphate is trans ported with excess sodium ions. Phosphate uptake was reduced by >50% i n mouse fibroblasts expressing amphotropic envelope glycoprotein, whic h binds to Ram-1, indicating that Ram-1 is a major phosphate transport er in these cells. RNA analysis shows wide but distinct tissue distrib utions, 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 controll ed by net phosphate accumulation. Accordingly, depletion of extracellu lar phosphate increased Ram-1 and Glvr-1 expression 3- to 5-fold. Thes e results suggest simple methods to modulate retroviral receptor expre ssion, with possible applications to human gene therapy.