Pannexin 3 functions as an ER Ca(2+) channel, hemichannel, and gap junction to promote osteoblast differentiation.
Pannexin 3 functions as an ER Ca(2+) channel, hemichannel, and gap junction to promote osteoblast differentiation.
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DOI：
10.1083/jcb.201101050
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发表时间：
2011-06-27
期刊：
影响因子：
--
通讯作者：
Yamada Y
中科院分区：
文献类型：
--
作者：
Ishikawa M;Iwamoto T;Nakamura T;Doyle A;Fukumoto S;Yamada Y
Pannexin 3是成骨细胞分化过程中Ca ~（2+）和ATP转运以及细胞间通讯的重要蛋白。然而，pannexins的细胞功能在很大程度上仍然未知。在这里，我们证明了泛连接蛋白3（Panx 3）促进成骨细胞的分化和跖骨的体外生长。在C2 C12细胞和原代颅骨细胞的成骨分化过程中诱导Panx 3表达，抑制这种内源性表达会抑制分化。Panx 3是内质网中一个独特的钙通道，通过嘌呤受体/磷酸肌醇3激酶（PI 3 K）/Akt信号通路激活，随后激活钙调素信号通路，促进细胞分化。Panx 3还形成半通道，其允许ATP释放到细胞外空间中并激活嘌呤能受体，随后激活PI 3 K-Akt信号传导。Panx 3还形成缝隙连接，并在细胞间传播Ca ~（2+）波。阻断Panx 3 Ca 2+通道和缝隙连接活性可抑制成骨细胞分化。因此，Panx 3似乎是一种新的调节剂，通过作为ER Ca 2+通道和半通道以及通过形成间隙连接来促进成骨细胞分化。
Pannexin 3 functions as an essential protein for Ca2+ and ATP transport and cell–cell communication during osteoblast differentiation The pannexin proteins represent a new gap junction family. However, the cellular functions of pannexins remain largely unknown. Here, we demonstrate that pannexin 3 (Panx3) promotes differentiation of osteoblasts and ex vivo growth of metatarsals. Panx3 expression was induced during osteogenic differentiation of C2C12 cells and primary calvarial cells, and suppression of this endogenous expression inhibited differentiation. Panx3 functioned as a unique Ca2+ channel in the endoplasmic reticulum (ER), which was activated by purinergic receptor/phosphoinositide 3-kinase (PI3K)/Akt signaling, followed by activation of calmodulin signaling for differentiation. Panx3 also formed hemichannels that allowed release of ATP into the extracellular space and activation of purinergic receptors with the subsequent activation of PI3K–Akt signaling. Panx3 also formed gap junctions and propagated Ca2+ waves between cells. Blocking the Panx3 Ca2+ channel and gap junction activities inhibited osteoblast differentiation. Thus, Panx3 appears to be a new regulator that promotes osteoblast differentiation by functioning as an ER Ca2+ channel and a hemichannel, and by forming gap junctions.
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影响因子：
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作者：
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DOI：
10.1073/pnas.2233464100
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