Pannexin1 is part of the pore forming unit of the P2X7 receptor death complex
Pannexin1 is part of the pore forming unit of the P2X7 receptor death complex
复制标题
DOI：
10.1016/j.febslet.2006.12.056
复制
发表时间：
2007-02-06
期刊：
影响因子：
3.5
通讯作者：
Dahl, Gerhard
中科院分区：
文献类型：
--
作者：
Locovei, Silviu;Scemes, Eliana;Dahl, Gerhard
嘌呤能受体P2X(7)是参与多种生理和病理过程的复杂信号机制的一部分。根据激活方案的不同，体内P2X(7)受体是非选择性阳离子通道或形成大孔，可介导凋亡细胞死亡。P2X(7)R在爪蟾卵母细胞中的表达只导致非选择性阳离子通道的形成。然而，本研究表明P2X(7)R与pannexin1在卵母细胞中的共表达导致了许多哺乳动物细胞中出现的复杂反应，包括长时间使用ATP导致细胞死亡。虽然阳离子通道活性对卡贝诺洛酮治疗具有抗性，但这种间隙连接和半通道阻断药物抑制了pannexin1/P2X(7)R共表达细胞中ATP诱导的电流。因此，pannexin1似乎是P2X(7)R信号复合体的渗透孔（或死亡受体通道）的分子底物。(c) 2007年欧洲生化学会联合会。Elsevier B.V.版权所有。
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 coexpression 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. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.