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

EMBO J. 2006 Nov 1;25(21):5071-82. doi: 10.1038/sj.emboj.7601378. Epub 2006 Oct 12.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caspase 1 / metabolism
  • Cell Line
  • Cell Membrane / metabolism*
  • Connexins / metabolism*
  • Humans
  • Interleukin-1beta / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Rats
  • Receptors, Purinergic P2 / metabolism*
  • Receptors, Purinergic P2X7
  • Signal Transduction / physiology*

Substances

  • Connexins
  • Interleukin-1beta
  • Nerve Tissue Proteins
  • P2RX7 protein, human
  • P2rx7 protein, rat
  • PANX1 protein, human
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X7
  • pannexin 1, rat
  • Caspase 1