Disease relevance of Slc20a2

• Ram-1 acts as both a sodium-dependent phosphate transporter and a receptor for amphotropic retroviruses [1].
• Results show that MDTF expressing these chimeras became susceptible to GALV, whereas cells expressing wild-type Pit2 remained resistant [2].
• We have constructed Moloney murine leukemia virus (MoMLV)-derived envelope glycoproteins (AMO) displaying an amino-terminal Ram-1-binding domain in which a variety of different amino acid spacers have been inserted between the displayed domain and the MoMLV surface (SU) subunit [3].
• We subjected a heterozygous 3-methylcholanthrene-induced murine sarcoma cell line to CTL immunoselection, selecting for the loss of a tumor-specific Ag, recognized antigen from MCA-induced tumor 1 (Ram1) [4].
• Previous studies established that infection of cells with A-MuLV resulted in the specific down-modulation of phosphate uptake mediated by Pit-2 and in resistance to superinfection with A-MuLV [5].

High impact information on Slc20a2

• The data are consistent with a model for receptor co-operativity in which binding to the targeted (Ram-1) receptor triggers conformational rearrangements of the envelope that lead to complete unmasking of the hidden Rec-1-binding domain, thereby facilitating its interaction with the viral (Rec-1) receptor which leads to optimal fusion triggering [3].
• An extreme example of receptor co-operativity was encountered when testing Ram-1-targeted AMOPRO envelopes with specific proline-rich interdomain spacers [3].
• We previously reported detectable Ram-1 in murine hematopoietic fetal liver cells (FLC) despite resistance of these cells to amphotropic retroviral transduction (infection) [1].
• 5. In addition, Ram-1 expression is detected only in more differentiated populations within FLC, day 14.5, and not in those highly enriched for stem cells, indicating developmental regulation of Ram-1 during murine hematopoiesis [1].
• We document here that Ram-1 expression is completely absent in murine yolk sac cells from days 9.5 through 13.5 of ontogeny and first appears at low levels in midgestational FLC between days 13.5 and 14 [1].

Chemical compound and disease context of Slc20a2

• Although the E36 line of Chinese hamster cells was reported to secrete the putative Pit2 inhibitor and to be sensitive to the inhibitory CHO factors, E36 cells are highly susceptible to both GALV and A-MLV in the absence of tunicamycin [6].

Biological context of Slc20a2

• Analysis of the progeny of two interspecies genetic crosses was used to establish the genetic map location of the mouse gene encoding this receptor, Ram1, within the proximal region of chromosome 8 [7].
• Up-regulation of the Pit-2 phosphate transporter/retrovirus receptor by protein kinase C epsilon [8].
• Higher density genetic analyses along with functional confirmation with an independently produced chromosome 4 loss of heterozygosity variant positioned the Ram1 locus to a distal 7.1 cM interval on chromosome 4 [4].
• This region of the mouse genome is rich in tumor-modifier genes and this positioning of Ram1 may thus provide insight into the genetic basis of 3-methycholanthrene-induced tumor Ags [4].
• Na+ -phosphate cotransport in mouse distal convoluted tubule cells: evidence for Glvr-1 and Ram-1 gene expression [9].

Anatomical context of Slc20a2

• These data demonstrate that (i) the normal resistance of FLC to amphotropic transduction is most likely due to an insufficient number of Ram-1 molecules for efficient retroviral recognition and binding, and (ii) Ram-1 can be upregulated by increasing the need for phosphate transport across the cell membrane [1].
• 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 [10].
• Moreover, expression of E36 Pit2 in CHO cells conferred tunicamycin-independent susceptibilities to both viruses [6].
• Overexpression of epsilon-epitope-tagged Pit-2 transporters in NIH 3T3 cells resulted in a marked increase in sodium-dependent P(i) uptake [5].
• Subcellular redistribution of Pit-2 P(i) transporter/amphotropic leukemia virus (A-MuLV) receptor in A-MuLV-infected NIH 3T3 fibroblasts: involvement in superinfection interference [5].

Associations of Slc20a2 with chemical compounds

• However, MolPit1 has isoleucine at this position and MolPit2 has glutamine at the corresponding position (position 522), thus breaking this consensus [2].
• The PKC-mediated activation of Pit-2 was blocked by pretreating cells with the pan-PKC inhibitor bisindolylmaleimide but not with the conventional PKC isotype inhibitor Gö 6976, suggesting that a novel PKC isotype is required to regulate Pit-2 [8].
• Extraction of murine fibroblastic NIH 3T3 cells in cold Triton X-100 showed the presence of the A-MLV receptor Pit2 in detergent-insoluble microdomains [11].
• For the amphotropic murine leukemia virus (MuLV), a 208-amino-acid amino-terminal fragment of the surface unit (SU) of the envelope glycoprotein is sufficient to bind to its receptor, Pit2 [12].

Other interactions of Slc20a2

• Further, the MolPit1 chimera was identical to Pit1 in efficiency, but the MolPit2 chimera proved substantially less efficient [2].
• This suggests that GALV can enter MMMol via not only the GALV receptor (MolPit1) but also the amphotropic murine leukemia virus receptor (MolPit2) [2].
• AMOPRO viruses could not enter cells expressing only Rec-1 or only Ram-1 but could efficiently infect cells co-expressing both receptors [3].
• Ram-1 messenger RNA expression was not affected by TGF-beta1 [13].

Analytical, diagnostic and therapeutic context of Slc20a2

• Molecular cloning of a murine type III sodium-dependent phosphate cotransporter (Pit-2) gene promoter [14].
• Assessment of amphotropic receptor (Pit-2) expression by RT-PCR demonstrated that all MSCs expressing the receptor were successfully transduced [15].
• The overexpressed epitope-tagged transporters were detected in cell lysates, by Western blot analysis using both epsilon-epitope- and GFP-specific antibodies as well as with Pit-2 antiserum [5].

References