title: Pannexin1 is part of the pore forming unit of the P2X(7) receptor death complex.
abstract: The purinergic receptor P2X(7) is part of a complex signaling mechanism participating in a variety of physiological and pathological processes. Depending on the activation scheme, P2X(7) receptors in vivo are non-selective cation channels or form large pores that can mediate apoptotic cell death. Expression of P2X(7)R in Xenopus oocytes results exclusively in formation of a non-selective cation channel. However, here we show that co-expression of P2X(7)R 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/P2X(7)R co-expressing cells. Thus, pannexin1 appears to be the molecular substrate for the permeabilization pore (or death receptor channel) recruited into the P2X(7)R signaling complex.
authors.affiliation: Department of Physiology and Biophysics, University of Miami School of Medicine, 1600 NW 10th Ave, Miami, FL 33136, USA.
authors.forename: Silviu
authors.initials: S
authors.lastname: Locovei
authors.forename: Eliana
authors.initials: E
authors.lastname: Scemes
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
authors.forename: David C
authors.initials: DC
authors.lastname: Spray
authors.forename: Gerhard
authors.initials: G
authors.lastname: Dahl
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017630:Connexins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism; D051379:Mice; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D058486:Receptors, Purinergic P2X7; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014981:Xenopus
chemical_list: D017630:Connexins; D007473:Ion Channels; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; C546468:P2RX7 protein, human; C546469:P2rx7 protein, mouse; C492764:PANX1 protein, human; D034741:RNA, Small Interfering; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate