Pannexin-1 mediates large pore formation and interleukin-1β release by the ATP-gated P2X7 receptor

Authors

  • Pablo Pelegrin,

  • Annmarie Surprenant

    Corresponding author
    1. Department of Biomedical Science, University of Sheffield, Sheffield, UK
    • Corresponding author. Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield, South Yorkshire S10 2TN, UK. Tel.: +44 114 222 2366; Fax: +44 114 222 2360; E-mail: a.surprenant@shef.ac.uk

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Abstract

P2X7 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-1β (IL-1β). It has not been known what this dye-uptake path is, or whether it is involved in downstream signalling to IL-1β 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-1β induced by P2X7 receptor activation.

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