Pannexin1 is part of the pore forming unit of the P2X7 receptor death complex

Silviu Locovei, Eliana Scemes, Feng Qiu, David C. Spray, Gerhard Dahl

Research output: Contribution to journalArticle

320 Scopus citations

Abstract

The purinergic receptor P2X7 is part of a complex signaling mechanism participating in a variety of physiological and pathological processes. Depending on the activation scheme, P2X7 receptors in vivo are non-selective cation channels or form large pores that can mediate apoptotic cell death. Expression of P2X7R in Xenopus oocytes results exclusively in formation of a non-selective cation channel. However, here we show that co-expression of P2X7R with pannexin1 in oocytes leads to the complex response seen in many mammalian cells, including cell death with prolonged ATP application. While the cation channel activity is resistant to carbenoxolone treatment, this gap junction and hemichannel blocking drug suppressed the currents induced by ATP in pannexin1/P2X7R co-expressing cells. Thus, pannexin1 appears to be the molecular substrate for the permeabilization pore (or death receptor channel) recruited into the P2X7R signaling complex.

Original languageEnglish (US)
Pages (from-to)483-488
Number of pages6
JournalFEBS letters
Volume581
Issue number3
DOIs
StatePublished - Feb 6 2007

Keywords

  • Ion channel
  • P2X
  • Pannexin
  • Pore
  • siRNA

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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