Intracellular trafficking pathways of Cx43 gap junction channels.
Intracellular trafficking pathways of Cx43 gap junction channels.
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DOI：
10.1016/j.bbamem.2017.05.018
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Shaw RM
中科院分区：
文献类型：
--
作者：
Epifantseva I;Shaw RM
间隙连接（GJ）通道，包括最常见的连接蛋白43（Cx43），通过促进相邻细胞之间的动作电位的快速传递而在可兴奋组织中具有基本作用。例如，在每次心跳期间的同步化由心肌细胞细胞-细胞边界处的这些离子通道调节。Cx43蛋白具有短的半衰期，并且这些蛋白的快速合成和及时递送到特定的亚结构域对于间隙连接的细胞组织和细胞内偶联的维持是至关重要的。缝隙连接运输的损伤导致患病心脏的危险并发症，例如心脏性猝死的心律失常。最近感兴趣的是与Cx43羧基末端的蛋白质-蛋白质相互作用。这些相互作用对Cx43的整个生命周期有重要影响，也有助于Cx43的运输以及可能的其他功能。我们正在学习，许多已知的非经典的作用，Cx43可以归因于最近确定的六个内源性Cx43截断异构体，这是由内部翻译产生的。总的来说，替代翻译是蛋白质组扩增和治疗药物开发的新前沿。这篇综述强调了最近发现的机制，在运输的间隙连接通道，参与其他蛋白质有助于提供通道的细胞-细胞边界，并了解新发现的替代翻译的Cx43生物学亚型的可能作用。
Gap Junction (GJ) channels, including the most common Connexin 43 (Cx43), have fundamental roles in excitable tissues by facilitating rapid transmission of action potentials between adjacent cells. For instance, synchronization during each heartbeat is regulated by these ion channels at the cardiomyocyte cell-cell border. Cx43 protein has a short half-life, and rapid synthesis and timely delivery of those proteins to particular subdomains are crucial for the cellular organization of gap junctions and maintenance of intracellular coupling. Impairment in gap junction trafficking contributes to dangerous complications in diseased hearts such as the arrhythmias of sudden cardiac death. Of recent interest are the protein-protein interactions with the Cx43 carboxy-terminus. These interactions have significant impact on the full length Cx43 lifecycle and also contribute to trafficking of Cx43 as well as possibly other functions. We are learning that many of the known non-canonical roles of Cx43 can be attributed to the recently identified six endogenous Cx43 truncated isoforms which are produced by internal translation. In general, alternative translation is a new leading edge for proteome expansion and therapeutic drug development. This review highlights recent mechanisms identified in the trafficking of gap junction channels, involvement of other proteins contributing to the delivery of channels to the cell-cell border, and understanding of possible roles of the newly discovered alternatively translated isoforms in Cx43 biology.
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影响因子：
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