P2RX7

Trimeric, ATP-gated non-selective cation channel of the P2X family and the receptor through which high concentrations of extracellular ATP are read as a danger signal. Each subunit has two transmembrane helices and a large disulphide-rich ectodomain; three subunits form the channel, with ATP binding at the subunit interfaces. P2X7 is distinguished from the other six P2X receptors by a low apparent ATP affinity, by the absence of desensitisation, and by an unusually long cytoplasmic C-terminus that carries a palmitoylated C-cys anchor and a zinc- and guanosine-nucleotide-binding cytoplasmic ballast. Opening admits sodium and calcium and allows potassium efflux; the fall in cytosolic potassium licenses NLRP3 inflammasome assembly, caspase-1 activation and release of mature interleukin-1 beta, which is the receptor's best-established physiological output. Sustained activation additionally causes membrane blebbing, phosphatidylserine exposure, cell shrinkage and eventually death - effects executed by downstream partners, notably the scramblase ANO6/TMEM16F and the channel pannexin-1, rather than by P2X7 itself. Expression is highest in cells of the myeloid lineage, including macrophages, monocytes, microglia and osteoclasts. Whether neurons express functional P2X7 is a long-running and unresolved controversy, contested on grounds of antibody specificity and pharmacological rigour even though cell-type-specific knockouts and human single-cell data have been used to argue for it; the dispute concerns which cells carry the receptor, not what the receptor does. A second unresolved question is whether prolonged activation dilates the P2X7 pore itself into a large conductance pathway, or whether the associated large-solute permeability belongs to pannexin-1.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.