Cell-surface receptors for gibbon ape leukemia virus and amphotropic murine retrovirus are inducible sodium-dependent phosphate symporters

Michael P. Kavanaugh, Daniel G. Miller, Weibin Zhang, Wendy Law, Susan L. Kozak, David Kabat, A. Dusty Miller

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)7071-7075
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number15
DOIs
StatePublished - Jul 19 1994

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Gibbon ape leukemia virus
Sodium-Phosphate Cotransporter Proteins
Cell Surface Receptors
Retroviridae
Phosphates
Fibroblasts
Phosphate Transport Proteins
Neurospora crassa
Xenopus laevis
Tissue Distribution
Genetic Therapy
Oocytes
Cations
Glycoproteins
Electrodes
Bone Marrow
Sodium
gibbon ape leukemia virus receptors
RNA
Ions

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Cell-surface receptors for gibbon ape leukemia virus and amphotropic murine retrovirus are inducible sodium-dependent phosphate symporters. / Kavanaugh, Michael P.; Miller, Daniel G.; Zhang, Weibin; Law, Wendy; Kozak, Susan L.; Kabat, David; Miller, A. Dusty.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 15, 19.07.1994, p. 7071-7075.

Research output: Contribution to journalArticle

Kavanaugh, Michael P. ; Miller, Daniel G. ; Zhang, Weibin ; Law, Wendy ; Kozak, Susan L. ; Kabat, David ; Miller, A. Dusty. / Cell-surface receptors for gibbon ape leukemia virus and amphotropic murine retrovirus are inducible sodium-dependent phosphate symporters. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 15. pp. 7071-7075.
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