Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
J Mol Cell Cardiol. 2019 Feb;127:194-203. doi: 10.1016/j.yjmcc.2018.12.013. Epub 2018 Dec 27.
Human vascular connexins (Cx37, Cx40, Cx43, and Cx45) can form various types of gap junction channels to synchronize vasodilation/constriction to control local circulation. Most of our knowledge on heterotypic gap junctions of these vascular connexins was from studies on rodent connexins. In human vasculature, the same four homolog connexins exist, but whether these human connexins can form heterotypic GJs as those of rodents have not been fully studied. Here we used in vitro expression system to study the coupling status and GJ channel properties of human heterotypic Cx37/Cx40, Cx37/Cx43, and Cx37/Cx45 GJs. Our results showed that Cx37/Cx43 and Cx37/Cx45 GJs, but not Cx37/Cx40 GJs, were functional and each with unique rectifying channel properties. The failure of docking between Cx37 and Cx40 could be rescued by designed Cx40 variants. Characterization of the heterotypic Cx37/Cx43 and Cx37/Cx45 GJs may help us in understanding the intercellular communication at the myoendothelial junction.
人类血管连接蛋白（Cx37、Cx40、Cx43 和 Cx45）可以形成各种类型的缝隙连接通道，以协调血管舒张/收缩来控制局部循环。我们对这些血管连接蛋白异质缝隙连接的大部分了解来自于对啮齿动物连接蛋白的研究。在人类血管中，存在相同的四种同源连接蛋白，但这些人类连接蛋白是否能像啮齿动物那样形成异质 GJ 尚未得到充分研究。在这里，我们使用体外表达系统研究了人源异质 Cx37/Cx40、Cx37/Cx43 和 Cx37/Cx45 GJ 的偶联状态和 GJ 通道特性。我们的结果表明，Cx37/Cx43 和 Cx37/Cx45 GJ 是功能性的，而 Cx37/Cx40 GJ 不是，并且每个都具有独特的整流通道特性。Cx37 和 Cx40 之间对接的失败可以通过设计的 Cx40 变体来挽救。异质 Cx37/Cx43 和 Cx37/Cx45 GJ 的特性可以帮助我们理解肌内皮连接点的细胞间通讯。
