Reactome | P2X7 mediates membrane pores that include pannexin-1

P2X7 mediates membrane pores that include pannexin-1

Stable Identifier

R-HSA-877198

Type

Reaction [uncertain]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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P2X7 mediates membrane pores that include pannexin-1

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At higher concentrations of extracellular ATP, the P2X7 channel acts as an inducer of nonselective macropores permeable to large (up to 800 Da) inorganic and organic molecules. These 'death complex' pores rapidly leads to complete collapse of ionic gradients, changing the cytosolic environment from high K/ low Na/ low Cl to low K/ high Na/ high Cl (Steinberg et al. 1987, Steinberg & Silverstein 1987, Kahlenberg & Dubyak 2004). The long carboxyl-terminal cytoplasmic domain of P2X7 (352-595) appears to be crucial for P2X7 pore formation (Cheewatrakoolpong et al. 2005, Adinolfi et al. 2005). P2X7 membrane pores were recently shown to include pannexin-1 (Locovei et al. 2007). Pannexins have low homology with the invertebrate innexin gap junction proteins, reported to form gap junction channels and also to function as hemi-gap junction channels that are sensitive to gap junction channel blockers (Bruzzone et al. 2003, 2005). The P2X7 receptor is generally accepted to be part of a multimeric complex, not fully characterized (Kim et al. 2001).

Literature References

PubMed ID	Title	Journal	Year
2182768	ATP-induced pore formation in the plasma membrane of rat peritoneal mast cells Tatham, PE, Lindau, M	J Gen Physiol	1990
18596211	P2X7 receptor-Pannexin1 complex: pharmacology and signaling Iglesias, R, Locovei, S, Roque, A, Alberto, AP, Dahl, G, Spray, DC, Scemes, E	Am J Physiol Cell Physiol	2008
450099	ATP induces nucleotide permeability in rat mast cells Cockcroft, S, Gomperts, BD	Nature	1979
17036048	Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor Pelegrin, P, Surprenant, A	EMBO J	2006