Characterization of novel Pannexin 1 isoforms from rat pituitary cells and their association with ATP-gated P2X channels.
Characterization of novel Pannexin 1 isoforms from rat pituitary cells and their association with ATP-gated P2X channels.
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DOI：
10.1016/j.ygcen.2011.08.019
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发表时间：
2011-11-01
影响因子：
2.7
通讯作者：
Stojilkovic, Stanko S.
中科院分区：
文献类型：
--
作者：
Li, Shuo;Tomic, Melanija;Stojilkovic, Stanko S.
我们以前的研究表明，Pannexin 1（Panx 1），最近发现的间隙连接蛋白家族的成员，在垂体中表达。在这里，我们调查的存在和表达模式的Panx 1亚型在垂体细胞中，它们在ATP释放的作用，以及它们与嘌呤能P2 X受体亚型是本地垂体细胞。除了全尺寸的Panx 1，称为Panx 1a，垂体细胞还表达两种新的较短的亚型，称为Panx 1c和Panx 1d，其形成反映了外显子2和4中存在选择性剪接位点。Panx 1c缺少Phe 108-Gln 180序列，P2 X1 d缺少Val 307-Cys 426 C末端序列。共聚焦显微镜和生物素标记显示，Panx 1a是在质膜上表达，而Panx 1c和Panx 1d显示细胞质定位时，作为同源蛋白表达。三种Panx 1同种型和Panx 2以任何组合形成同聚和异聚复合物。这些剪接形式也可以与ATP门控的P2 X2、P2 X3、P2 X4和P2 X7受体通道物理结合。当与Panx 1c或Panx 1d共表达时，AtT-20永生化垂体细胞中Panx 1a介导的ATP释放减弱。这些结果表明，Panx 1c和Panx 1d可能作为显性负效应器，通过形成异聚体通道来调节Panx 1a的功能。Panx 1表达和关联的复杂模式也可以定义这些通道在共表达两种蛋白质的细胞类型中的P2 X依赖性作用。
Our previous studies have showed that Pannexin 1 (Panx1), a member of a recently discovered family of gap junction proteins, is expressed in the pituitary gland. Here we investigated the presence and expression pattern of Panx1 isoforms in pituitary cells, their roles in ATP release, and their association with purinergic P2X receptor subtypes that are native to pituitary cells. In addition to the full-size Panx1, termed Panx1a, pituitary cells also express two novel shorter isoforms, termed Panx1c and Panx1d, which formation reflects the existence of alternative splicing sites in exons 2 and 4. Panx1c is lacking the Phe108-Gln180 sequence and P2X1d is missing the Val307-Cys426 C-terminal end sequence. Confocal microscopy and biotin labeling revealed that Panx1a is expressed in the plasma membrane, whereas Panx1c and Panx1d show the cytoplasmic localization when expressed as homomeric proteins. The three Panx1 isoforms and Panx2 form homomeric and heteromeric complexes in any combination. These splice forms can also physically associate with ATP-gated P2X2, P2X3, P2X4, and P2X7 receptor channels. The Panx1a-mediated ATP release in AtT-20 immortalized pituitary cells is attenuated when co-expressed with Panx1c or Panx1d. These results suggest that Panx1c and Panx1d may serve as dominant-negative effectors to modulate the functions of Panx1a through formation of heteromeric channels. The complex patterns of Panx1 expression and association could also define the P2X-dependent roles of these channels in cell types co-expressing both proteins.
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作者：
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发表时间：
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影响因子：
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