The
cell surface receptor for gibbon ape leukemia virus (Glvr-1) was recently demonstrated to serve normal cellular functions as a
sodium-dependent
phosphate (NaPi) transporter. This
protein belongs to a newly identified
phosphate transporter/retrovirus receptor gene family distinct from renal type I and II NaPi transporters. Although
inorganic phosphate (Pi) transport is an important function of osteoblasts and of the matrix vesicles produced by these cells in the context of bone matrix calcification, the molecular identity of the NaPi transport system(s) present in this cell type is still unknown. In contrast to Pi uptake mediated by renal NaPi transporters, the activities of both the osteoblastic transport system and
Glvr-1 are decreased at alkaline pH, and this observation led us to investigate expression of this transporter in human SaOS-2
osteosarcoma cells. Northern blotting analysis revealed the presence of a 4-kilobase
Glvr-1 transcript. The expression of
Glvr-1 messenger RNA (
mRNA) was increased in response to
insulin-like growth factor I (
IGF-I). Associated with this effect, a selective, dose- and time-dependent stimulation of NaPi transport was observed.
Actinomycin D and
cycloheximide abolished the increase in NaPi transport, which thus appeared to be dependent on
RNA and
protein synthesis. The increase in
Glvr-1 mRNA induced by
IGF-I was dose dependent and transient, peaking after 4 h (approximately 4-fold increase in response to 10(-7) M
IGF-I). It preceded the maximal expression of NaPi transport stimulation (173-235% of control), which was observed after 18-24 h. Induction of
Glvr-1 mRNA expression by
IGF-I was inhibited by
actinomycin D, suggesting that this effect was related to an increase in gene transcription. The stability of
Glvr-1 mRNA was not altered by
IGF-I, and
Glvr-1 mRNA induction did not require the synthesis of new
proteins. These data demonstrate for the first time regulated expression of
mRNA encoding the type III NaPi transporter
Glvr-1 in osteoblast-like cells. They also suggest that this new transporter family may be involved in Pi handling in osteogenic cells and in its regulation by osteotropic factors.