Connexin43 and pannexin1 channels in osteoblasts: who is the "hemichannel"?

Connexin43 and pannexin1 channels in osteoblasts: who is the "hemichannel"?
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DOI:
10.1007/s00232-012-9462-2
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发表时间:
2012-07
影响因子:
2.4
通讯作者:
Spray, David C.
Spray, David C.
中科院分区:
生物学4区
文献类型:
--
作者:
Thi, Mia M.;Islam, Shalena;Suadicani, Sylvia O.;Spray, David C.

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在涉及大离子和信号分子的流入和释放的过程中,成骨细胞感知机械刺激并对其做出反应。由连接蛋白43(Cx43)形成的非对位缝隙连接半通道被认为是这种交换的主要途径,特别是在骨细胞中释放ATP和前列腺素E2(PGE2)。然而,我们发现,Cx43缺失的成骨细胞没有改变机械诱导的PGE2释放和ATP诱导的YoPro染料摄取。相反,在P2X7受体(P2X7R)缺失的成骨细胞中,由于流体剪切力的反应,PGE2的释放被取消,野生型细胞经P2X7R或PAnnexin1(Panx1)通道阻滞剂处理后,ATP诱导的染料摄取被减弱。这些数据表明,Panx1通道与P2X7R结合,可能形成一个分子复合体,在成骨细胞机械信号转导中发挥半通道功能。
Osteoblasts sense and respond to mechanical stimuli in a process involving influx and release of large ions and signaling molecules. Unapposed gap junction hemichannels formed of connexin43 (Cx43) have been proposed as a major route for such exchange, and in particular for release of ATP and prostaglandin E2 (PGE2) in osteocytes. However, we have found that Cx43-null osteoblasts have unaltered mechanically-induced PGE2 release and ATP-induced YoPro dye uptake. In contrast, PGE2 release in response to fluid shear stress is abolished in P2X7 receptor (P2X7R) null osteoblasts and ATP-induced dye uptake is attenuated following treatment of wildtype cells with a P2X7R or Pannexin1 (Panx1) channel blocker. These data indicate that Panx1 channels, in concert with P2X7R, likely form a molecular complex that performs the hemichannel function in osteoblast mechanosignaling.
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