Disease relevance of P2RX5

• P2X5 and P2Y2 receptors were heavily expressed in basal cell carcinomas and squamous cell carcinomas [1].
• By contrast, LCLs expressed several dominant P2 receptors--P2X4, P2X5, and P2Y11--in amounts similar to those seen in B cells infected with EBV for 2 weeks [2].
• A frameshift polymorphism in P2X5 elicits an allogeneic cytotoxic T lymphocyte response associated with remission of chronic myeloid leukemia [3].
• These findings illustrate that the P2X5-encoded mHAg LRH-1 could be an attractive target for specific immunotherapy to treat hematological malignancies recurring after allogeneic stem cell transplantation [3].

High impact information on P2RX5

• Here, we have used genetic linkage analysis to identify a novel mHAg, designated lymphoid-restricted histocompatibility antigen-1 (LRH-1), which is encoded by the P2X5 gene and elicited an allogeneic CTL response in a patient with chronic myeloid leukemia after donor lymphocyte infusion [3].
• P2X5 Subunit Assembly Requires Scaffolding by the Second Transmembrane Domain and a Conserved Aspartate [4].
• When expressed in Xenopus oocytes, hetero-oligomeric P2X1+5 ATP receptors were characterized by slowly desensitizing currents highly sensitive to the agonist alpha,beta-methylene ATP (EC50 = 1.1 microM) and to the antagonist trinitrophenyl ATP (IC50 = 64 nM), observed with neither P2X1 nor P2X5 alone [5].
• Reversal potential measurements showed that the human P2X5 receptor was permeable to calcium (PCa/PNa = 1.5) and N-methyl-d-glucamine (NMDG) (PNMDG/PNa = 0.4); it was also permeable to chloride (PCl/PNa = 0.5) but not gluconate (Pgluc/PNa = 0.01) ions [6].
• In cells expressing the homomeric P2X1 receptor, 30 microM alpha,beta-methylene ATP (alpha,beta-me-ATP) evoked robust currents that completely desensitized in less than 1 sec, whereas alpha,beta-me-ATP failed to evoke current in cells expressing the homomeric P2X5 receptor [7].

Biological context of P2RX5

• There was a significant decrease in cell number as a result of treatment with the P2X5 receptor agonist ATPgammaS (p<0.001) and the P2X7 receptor agonist BzATP (p<0.001) [8].

Anatomical context of P2RX5

• P2X5 receptors double labeled with differentiated fetal keratinocytes that were positive for cytokeratin K10, suggesting a role in differentiation [9].
• In blood leukocytes, transcripts of P2X5, P2X7 and all P2Y receptors, except for P2Y6, receptor were found [10].

Regulatory relationships of P2RX5

• Further, the EC50 for alpha,beta-me-ATP was greater in cells expressing both P2X1 and P2X5 than in cells expressing P2X1 alone (5 and 1.6 microM, respectively) [7].

Analytical, diagnostic and therapeutic context of P2RX5

• Data from in situ hybridization studies suggest that P2X1 and P2X5 may also co-assemble [7].
• Heteromeric assembly was confirmed using a co-immunoprecipitation assay of epitope-tagged P2X1 and P2X5 subunits [7].
• We identified the P2X subtypes present in BAECs using RT-PCR. mRNA was present for only three of seven family members: P2X4, P2X5, and P2X7 [11].

References