Disease relevance of P2RXL1

• The results suggest that P2XM may play a significant role in the proliferation and/or differentiation of skeletal muscle cells and that its altered expression may be involved in the development of some sarcomas [1].
• P2XM was localized to chromosomal band 22q11, where frequent loss of heterozygosity has been observed in rhabdoid tumors [1].

High impact information on P2RXL1

• The assembly of P2X4 with P2X6 subunits results from subunit-dependent interactions, as shown by their specific copurification from HEK-293 cells transiently transfected with various epitope-tagged P2X channel subunits [2].
• Hence, we designated the gene P2XM (P2X specifically expressed in skeletal muscle) [1].
• When this region is removed, or when charge is added to it, P2X6 forms homotrimeric assemblies, undergoes complex glycosylation and is delivered to the plasma membrane, albeit less efficiently than the P2X2 receptor [3].
• We propose that the N terminus of the P2X6 subunit contributes to a mechanism that prevents the inappropriate export and plasma membrane expression of nonfunctional P2X receptors [3].
• An uncharged region within the N terminus of the P2X6 receptor inhibits its assembly and exit from the endoplasmic reticulum [3].

Biological context of P2RXL1

• We demonstrate here that the coexpression of P2X4 and P2X6 subunits in Xenopus oocytes leads to the generation of a novel pharmacological phenotype of ionotropic ATP receptors [2].
• In this study, we used a combination of immunocytochemistry, surface biotinylation, and atomic force microscopy to investigate the assembly and trafficking of the P2X6 subunit, both alone and as part of a heteromer [3].
• Co-labelling experiments at the confocal and electron microscopy levels revealed that P2X4 and P2X6 receptors are strongly co-localised with the cell adhesion molecule VE-cadherin [4].
• Frequent loss of expression or aberrant alternative splicing of P2XM, a p53-inducible gene, in soft-tissue tumours [5].
• P2 receptors in human heart: upregulation of P2X6 in patients undergoing heart transplantation, interaction with TNFalpha and potential role in myocardial cell death [6].

Anatomical context of P2RXL1

• We investigated the expression of P2X4 and P2X6 receptors on human umbilical vein endothelial cells (HUVECs) and found that both P2X receptor subtypes on plasma membranes are largely restricted to areas of cell-cell contact [4].
• Disruption of microfilaments, microtubules and integrin-mediated adhesion or stimulation of P2 receptors with ATP did not alter P2X4 and P2X6 receptor expression on HUVEC plasma membranes [4].
• We conclude that P2X4 and P2X6 receptors are associated with VE-cadherin at HUVEC adherens junctions [4].
• In control myofibres there was no staining for any P2X subtype studied here, although P2X1 stained the smooth muscle of the blood vessels and P2X6 nerves and the tunica intima in small arteries [7].

Associations of P2RXL1 with chemical compounds

• Membraneous P2X4 and P2X6 receptors resisted extraction with Triton-X 100, whereas cytoplasmic P2X receptors were Triton-X 100 soluble [4].
• Purinergic receptor agonists increased I(sc) with a potency order of ATP > 2'- and 3'-O-(4-benzoyl-benzoyl)adenosine 5'-triphosphate alpha,beta-methyleneadenosine 5'-triphosphate in both OSC and VTC [8].

Other interactions of P2RXL1

• We failed to clone P2X1 and P2X6 genes [9].
• P2X6 receptors do not express readily, and P2X7 receptors correspond closely in their properties to P2Z [10].
• P2X4 and P2X6 receptors associate with VE-cadherin in human endothelial cells [4].

References