Vanden Abeele Fabien, Bidaux Gabriel, Gordienko Dmitri, Beck Benjamin, Panchin Yuri V, Baranova Ancha V, Ivanov Dmitry V, Skryma Roman, Prevarskaya Natalia
Institut National de la Santé et de la Recherche Médicale, U800, Equipe labellisée par la Ligue Contre le Cancer, Universite des Sciences et Technologies de Lille, Villeneuve d'Ascq Cedex, F-59655 France.
J Cell Biol. 2006 Aug 14;174(4):535-46. doi: 10.1083/jcb.200601115.
Although human pannexins (PanX) are homologous to gap junction molecules, their physiological function in vertebrates remains poorly understood. Our results demonstrate that overexpression of PanX1 results in the formation of Ca(2+)-permeable gap junction channels between adjacent cells, thus, allowing direct intercellular Ca(2+) diffusion and facilitating intercellular Ca(2+) wave propagation. More intriguingly, our results strongly suggest that PanX1 may also form Ca(2+)-permeable channels in the endoplasmic reticulum (ER). These channels contribute to the ER Ca(2+) leak and thereby affect the ER Ca(2+) load. Because leakage remains the most enigmatic of those processes involved in intracellular calcium homeostasis, and the molecular nature of the leak channels is as yet unknown, the results of this work provide new insight into calcium signaling mechanisms. These results imply that for vertebrates, a new protein family, referred to as pannexins, may not simply duplicate the connexin function but may also provide additional pathways for intra- and intercellular calcium signaling and homeostasis.
尽管人类泛连接蛋白（PanX）与间隙连接分子同源，但其在脊椎动物中的生理功能仍知之甚少。我们的结果表明，PanX1的过表达导致相邻细胞之间形成Ca(2+)可渗透的间隙连接通道，从而允许细胞间Ca(2+)直接扩散并促进细胞间Ca(2+)波传播。更有趣的是，我们的结果强烈表明，PanX1也可能在内质网（ER）中形成Ca(2+)可渗透通道。这些通道导致ER Ca(2+)泄漏，从而影响ER Ca(2+)负荷。由于泄漏仍然是细胞内钙稳态所涉及的那些过程中最神秘的，并且泄漏通道的分子性质尚不清楚，这项工作的结果为钙信号传导机制提供了新的见解。这些结果意味着，对于脊椎动物来说，一个被称为泛连接蛋白的新蛋白质家族可能不仅仅是重复连接蛋白的功能，还可能为细胞内和细胞间的钙信号传导及稳态提供额外的途径。
