P2RX7

502718439ENSG00000089041ENSMUSG00000029468Q99572Q9Z1M0NM_002562NM_177427NM_001038839NM_001038845NM_001038887NM_001284402NM_011027NP_002553NP_001033928NP_001033934NP_001033976NP_001271331NP_035157Purinergic signallingNucleoside transportersP2X purinoceptor 7 is a protein that in humans is encoded by the P2RX7 gene. P2X purinoceptor 7 is a protein that in humans is encoded by the P2RX7 gene. The product of this gene belongs to the family of purinoceptors for ATP. Multiple alternatively spliced variants which would encode different isoforms have been identified although some fit nonsense-mediated decay criteria. The receptor is found in the central and peripheral nervous systems, in microglia, in macrophages, in uterine endometrium, and in the retina. The P2X7 receptor also serves as a pattern recognition receptor for extracellular ATP-mediated apoptotic cell death, regulation of receptor trafficking, mast cell degranulation, and inflammation. The P2X7 subunits can form homomeric receptors only with a typical P2X receptor structure.The P2X7 receptor is a ligand-gated cation channel that opens in response to ATP binding and leads to cell depolarization. The P2X7 receptor requires higher levels of ATP than other P2X receptors; however, the response can be potentiated by reducing the concentration of divalent cations such as calcium or magnesium. Continued binding leads to increased permeability to N-methyl-D-glucamine (NMDG+). P2X7 receptors do not become desensitized readily and continued signaling leads to the aforementioned increased permeability and an increase in current amplitude. P2X7 receptors respond to BzATP more readily than ATP. ADP and AMP are weak agonists of P2X7 receptors, but a brief exposure to ATP can increase their effectiveness. Glutathione has been proposed to act as a P2X7 receptor agonist when present at milimolar levels, inducing calcium transients and GABA release from retinal cells. The P2X7 receptor current can be blocked by zinc, calcium, magnesium, and copper. P2X7 receptors are sensitive to pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) and relatively insensitive to suramin, but the suramin analog, NF279, is much more effective. Oxidized ATP (OxATP) and Brilliant Blue G has also been used for blocking P2X7 in inflammation. Other blockers include the large organic cations calmidazolium (a calmodulin antagonist) and KN-62 (a CaM kinase II antagonist). In microglia, P2X7 receptors are found mostly on the cell surface. Conserved cysteine residues located in the carboxyl terminus seem to be important for receptor trafficking to the cell membrane. These receptors are upregulated in response to peripheral nerve injury. In melanocytic cells P2X7 gene expression may be regulated by MITF. Activation of the P2X7 receptor by ATP leads to recruitment of pannexin pores which allow small molecules such as ATP to leak out of cells. This allows further activation of purinergic receptors and physiological responses such a spreading cytoplasmic waves of calcium. Moreover, this could be responsible for ATP-dependent lysis of macrophages through the formation of membrane pores permeable to larger molecules.