Disease relevance of SLC20A1

• Growth plate chondrocyte hypertrophy is associated with expression of the type III sodium-dependent inorganic phosphate (Pi) cotransporter phosphate transporter/retrovirus receptor 1 (PiT-1) [1].
• This study was undertaken to test the hypothesis that IL-8 promotes chondrocyte hypertrophy by modulating chondrocyte PiT-1 expression and sodium-dependent Pi uptake, and to assess differential roles in this activity [1].
• CONCLUSION: Our results link low-grade IL-8-mediated cartilaginous inflammation in OA to altered chondrocyte differentiation and disease progression through PiT-1 expression and sodium-dependent Pi uptake mediated by CXCR1 signaling [1].
• We have identified two Streptococcus pneumoniae genetic loci, pit1 and pit2, encoding homologues of ABC iron transporters that are required for iron uptake by this organism [2].
• A stretch of nine amino acids (region A) in the predicted fourth extracellular loop was previously shown to be critical for the function of Glvr1 as receptor for GALV and FeLV-B [3].

High impact information on SLC20A1

• RNA analysis shows wide but distinct tissue distributions, with Glvr-1 expression being highest in bone marrow and Ram-1 in heart [4].
• Overexpression of Ram-1 severely repressed Glvr-1 synthesis in fibroblasts, suggesting that transporter expression may be controlled by net phosphate accumulation [4].
• By expression in Xenopus laevis oocytes and in mammalian cells, we have identified Glvr-1 and Ram-1 as sodium-dependent phosphate symporters [4].
• The increase in transduction with PG13 vectors correlated with Northern blotting and reverse transcription-polymerase chain reaction studies that indicated that both K562 cells and the LAD EBV B cells express transcripts for the gibbon ape leukemia virus receptor at higher levels than for the amphotropic virus receptor [5].
• Type III sodium-dependent phosphate (NaP(i)) cotransporters, Pit1 and Pit2, have been assigned housekeeping P(i) transport functions and suggested involved in chondroblastic and osteoblastic mineralization and ectopic calcification [6].

Biological context of SLC20A1

• In addition, the regulation of Glvr-1 gene expression also has potential applications to gene therapy, since retroviral vectors carrying gibbon ape leukemia virus envelope proteins are used for gene delivery into different cell types [7].
• Characterization of the human Glvr-1 phosphate transporter/retrovirus receptor gene and promoter region [7].
• The aim of this study was thus to clone the human Glvr-1 gene in order to describe its structure and its promoter region.Our results indicate that the Glvr-1 gene consists of 11 exons and 10 introns spread over 18kb of genomic DNA [7].
• Moreover, the downregulation of 10A1 receptor function by changes in region A of human Pit1 indicates that this region is also involved in 10A1 entry [8].
• These transporters, called PiT-1 and PiT-2, respectively, are approximately 59% identical in amino acid sequence and are members of a gene family distinct from the renal type I and type II NaPi sodium-dependent phosphate transporters [9].

Anatomical context of SLC20A1

• Rapid amplification of cDNA ends (5'-RACE) suggests that, in human SaOS-2 osteoblast-like cells, transcription of Glvr-1 is initiated at multiple sites, mostly located between bp 32 and 50 of the published cDNA sequence, which was initially obtained from HL-60 cells [7].
• However, at least in one cell line it used Pit1 more efficiently for entry [10].
• We then analyzed whether this enhanced expression of GLVR-1 correlated with increased infectivity of lymphocytes by retroviral vectors that utilize the GALV envelope compared to those that use the amphotropic envelope [11].
• The superior transduction efficacy of CD8+ T cells by MuLV-10A1 correlates with a longer half-life of this pseudotype in comparison with A-MuLV and, as shown by interference analysis with the human T cell line HUT78, by the utilization of both the A-MuLV receptor (Pit2) and the GaLV receptor (Pit1) for cell entry [12].
• Hormonal treatment or P(i) starvation of tooth germs in vitro did not alter Pit2 levels or patterns of expression, indicating mechanisms of regulation different from those of PiT-1 or other cell types [13].

Associations of SLC20A1 with chemical compounds

• However, the substitution of serine for methionine at position 138 (S138M) in a Pit1 chimera containing domain II of Pit2 resulted in a 1,000-fold reduction in A-MuLV receptor function [14].
• Thus the presence of an aspartic acid in either of the PiT family signature sequences is critical for the Na+-dependent P(i) transport function of human PiT2 [15].
• 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 [16].
• About 25% of nitrite uptake occurred on the sodium-dependent phosphate transporter and the rest as diffusion of nitrous acid or other species across the plasma membrane [17].
• Further, transport was significantly decreased by the addition to the incubation medium of phosphonoformic acid, a sodium-dependent phosphate transporter inhibitor, and severely inhibited under sodium-free conditions [18].

Regulatory relationships of SLC20A1

• BACKGROUND: Parathyroid hormone (PTH) rapidly down-regulates type IIa sodium-dependent phosphate transporter (NaPi-IIa) via an endocytic pathway [19].

Other interactions of SLC20A1

• These characteristics were different from those reported for hNaPi-3 and hPiT-1 in other systems [20].
• Human PiT1 (PiT1), another type III sodium phosphate cotransporter, is a highly related protein that functions as a receptor for gibbon ape leukemia virus but not for A-MuLV [21].
• The sodium-dependent phosphate transporter (HOST5/SLC34A2) expression was associated with increased differentiation in ovarian serous tumors [22].
• These changes occur early after exposure to high phosphate levels and seem to be mediated by a sodium-dependent phosphate co-transporter, Pit-1 (Glvr-1) [23].

Analytical, diagnostic and therapeutic context of SLC20A1

• The gibbon ape leukemia virus (GaLV) and the amphotropic murine leukemia virus (A-MuLV) infect human cells via specific receptors, Pit1 and Pit2, respectively. mRNA levels of these receptors were determined by Northern analysis and for Pit2 in addition by quantitative RT-PCR [10].
• A cDNA fragment specific for the rhesus macaque gibbon ape leukemia virus (GaLV) receptor (Glvr-1) was isolated by polymerase chain reaction (PCR) amplification and oligonucleotide primers specific for human Glvr-1 and a cDNA library derived from rhesus macaque brain [24].
• Antibody specificity and molecular size of Glvr-1/Ram-1-related proteins were assayed by Western blot [25].

References