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PMID: 17240370 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Pannexin1 is part of the pore forming unit of the P2X(7) receptor death complex.

FEBS letters ·Vol. 581 ·No. 3 ·2007-02-06 ·Pages 483-8

Locovei S, Scemes E, Qiu F, Spray DC, Dahl G

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.

MeSH Terms
Adenosine Triphosphate/pharmacology Animals Base Sequence Cell Line Connexins/chemistry,genetics,metabolism Female Humans In Vitro Techniques Ion Channels/metabolism Mice Multiprotein Complexes Nerve Tissue Proteins Oocytes/drug effects,metabolism RNA, Small Interfering/genetics Rats Receptors, Purinergic P2/chemistry,genetics,metabolism Receptors, Purinergic P2X7 Recombinant Proteins/chemistry,genetics,metabolism Xenopus
Chemicals
Connexins Ion Channels Multiprotein Complexes Nerve Tissue Proteins P2RX7 protein, human P2rx7 protein, mouse PANX1 protein, human RNA, Small Interfering Receptors, Purinergic P2 Receptors, Purinergic P2X7 Recombinant Proteins Adenosine Triphosphate
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Locovei Silviu
Department of Physiology and Biophysics, University of Miami School of Medicine, 1600 NW 10th Ave, Miami, FL 33136, USA.
Scemes Eliana
Qiu Feng
Spray David C
Dahl Gerhard
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Article Info
Journal
FEBS letters
Abbr.
FEBS Lett
ISSN
0014-5793
DOI
10.1016/j.febslet.2006.12.056
Published
2007-02-06
Epub
2007-00-16
Pages
483-8
Language
English
Region
England
NLM ID
0155157
PMCID
PMC1868681
Subset
IM
Grants
NINDS NIH HHS · NS-41282 · United States
NIGMS NIH HHS · GM-48610 · United States
NINDS NIH HHS · NS-41023 · United States
NINDS NIH HHS · R01 NS041023 · United States
NIGMS NIH HHS · R01 GM048610 · United States
External Links
PubMed source DOI: 10.1016/j.febslet.2006.12.056 PMC Full Text View journal details
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