Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor.
P2X(7) receptors are ATP-gated cation channels; their activation in macrophage also leads to rapid opening of a membrane pore permeable to dyes such as ethidium, and to release of the pro-inflammatory cytokine, interleukin-1beta (IL-1beta). It has not been known what this dye-uptake path is, or whether it is involved in downstream signalling to IL-1beta release. Here, we identify pannexin-1, a recently described mammalian protein that functions as a hemichannel when ectopically expressed, as this dye-uptake pathway and show that signalling through pannexin-1 is required for processing of caspase-1 and release of mature IL-1beta induced by P2X(7) receptor activation.
Pelegrin
Pablo
P
Department of Biomedical Science, University of Sheffield, Sheffield, UK.
Surprenant
Annmarie
A
D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D015398:Signal Transduction / Q000502:physiology*
D017630:Connexins; D053583:Interleukin-1beta; D009419:Nerve Tissue Proteins; C546468:P2RX7 protein, human; C546470:P2rx7 protein, rat; C492764:PANX1 protein, human; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; C479936:pannexin 1, rat; D020170:Caspase 1