Disease relevance of Slc20a1

• These receptors include CD4 for human immunodeficiency virus, Rec-1 for murine ecotropic virus, and GLVR1 for gibbon ape leukemia virus [1].
• The mouse homolog of the Gibbon ape leukemia virus (GALV) receptor (Glvr-1) was mapped to mouse Chromosome 2 (Chr 2) by Southern blot analysis of somatic cell hybrids and positioned on this chromosome using an interspecies genetic cross [2].
• In vivo expression of transcripts encoding the Glvr-1 phosphate transporter/retrovirus receptor during bone development [3].
• Amphotropic murine leukemia virus (A-MuLV) utilizes the PiT2 sodium-dependent phosphate transporter as its cell surface receptor to infect mammalian cells [4].
• Ectopic expression of the feline PiT-1 in guinea pig cells, which are non-permissive to feline leukemia virus (FeLV), subgroup B virus, conferred susceptibility to FeLV-B infection confirming the functional ability of the cloned product to serve as a receptor for a natural retrovirus of the homologous species [5].

High impact information on Slc20a1

• Ram-1 acts as both a sodium-dependent phosphate transporter and a receptor for amphotropic retroviruses [6].
• The sodium-dependent phosphate transporter, Pho-4, from the filamentous fungus Neurospora crassa is distantly related to Pit1 and -2, showing an amino acid identity of only 35% to Pit1 in the putative extracellular loops [7].
• The three type C retroviruses, gibbon ape leukemia virus (GALV), simian sarcoma-associated virus (SSAV), and feline leukemia virus subgroup B (FeLV-B), infect human cells by interacting with the same cell surface receptor, GLVR1 [8].
• Glvr-1 RNA is most abundant in mouse brain and thymus, although it is present in all tissues examined [9].
• In order to assess the relationship between GLVR1 and other retroviral receptors, we mapped the chromosome location of GLVR1 in human and mouse [1].

Chemical compound and disease context of Slc20a1

• Strikingly, the amino acid sequence of the fourth extracellular loop, which is critical for GALV surface glycoprotein binding, has complete identity between the human and feline PiT-1s, while the mouse PiT-1, non-functional for GALV entry, is quite divergent [5].

Biological context of Slc20a1

• Glvr-1 was then mapped in the mouse by interspecies backcrosses and found to map to chromosome 2 in a region of linkage conservation with human chromosome 2 [1].
• To investigate whether Glvr-1 and Rec-2 could be the same gene, we sought evidence for sequence homology between the env- genes of their respective viruses [2].
• This pattern of Glvr-1 mRNA expression was maintained throughout embryonic development until after birth [3].
• In conclusion, the Glvr-1 phosphate transporter is selectively expressed in a subset of hypertrophic chondrocytes during endochondral bone formation, in a region where matrix mineralization proceeds [3].
• Na+ -phosphate cotransport in mouse distal convoluted tubule cells: evidence for Glvr-1 and Ram-1 gene expression [10].

Anatomical context of Slc20a1

• GLVR1 was found to map to human chromosome 2q11-q14 by in situ hybridization and somatic-cell hybrid analysis [1].
• No Glvr-1 transcripts were detected in fully differentiated hypertrophic chondrocytes [3].
• A hybridization signal for Glvr-1 was specifically observed in a subset of hypertrophic chondrocytes and could not be detected in osteoblasts [3].
• To address the relevance of these findings in the context of bone formation in vivo and, in particular, in relation to matrix calcification, we investigated expression of the Glvr-1 transporter by in situ hybridization in developing embryonic murine metatarsals, using human Glvr-1 cDNA as a probe [3].
• Rafts have been suggested to be pre-caveolae and we here investigate whether A-MLV initially binds to its receptor Pit2, a sodium-dependent phosphate transporter, in rafts or caveolae or outside these cholesterol-rich microdomains [11].

Physical interactions of Slc20a1

• In this study, we investigated the effect of TGF-beta1 on inorganic phosphate (Pi) transport and on expression of the type III Pi carriers Glvr-1 and Ram-1 in murine ATDC5 chondrocytes [12].

Regulatory relationships of Slc20a1

• In conclusion, TGF-beta1 stimulates Pi transport and Glvr-1 expression in chondrocytes, suggesting that, like proliferation, differentiation, and matrix synthesis, Pi handling is subject to regulation by TGF-beta3 family members in bone-forming cells [12].

Other interactions of Slc20a1

• Npt2 mRNA was localized to proximal tubules in the renal outer cortex, whereas Glvr-1 transcripts were detected throughout the kidney by in situ hybridization [13].
• Glvr-1 thus likely mediates at least part of the increase in Pi uptake induced by TGF-beta1 [12].
• Degradation of Npt-1 or Glvr-1 mRNAs induced by corresponding antisense oligonucleotides had no effect on Pi transport, which was subsequently measured in oocytes [14].

Analytical, diagnostic and therapeutic context of Slc20a1

• Consistently, Northern blotting analysis showed a dose-dependent increase in Glvr-1 messenger RNA expression in response to TGF-beta1, which preceded the maximal stimulation of Pi transport by several hours [12].

References