PDF(Pubmed)
Abstract：
Over 35 years ago the cell biology community was introduced to connexins as the subunit employed to assemble semicrystalline clusters of intercellular channels that had been well described morphologically as gap junctions. The decade that followed would see knowledge of the unexpectedly large 21-member human connexin family grow to reflect unique and overlapping expression patterns in all organ systems. While connexin biology initially focused on their role in constructing highly regulated intercellular channels, this was destined to change as discoveries revealed that connexin hemichannels at the cell surface had novel roles in many cell types, especially when considering connexin pathologies. Acceptance of connexins as having bifunctional channel properties was initially met with some resistance, which has given way in recent years to the premise that connexins have multifunctional properties. Depending on the connexin isoform and cell of origin, connexins have wide-ranging half-lives that vary from a couple of hours to the life expectancy of the cell. Diversity in connexin channel characteristics and molecular properties were further revealed by X-ray crystallography and single-particle cryo-EM. New avenues have seen connexins or connexin fragments playing roles in cell adhesion, tunneling nanotubes, extracellular vesicles, mitochondrial membranes, transcription regulation, and in other emerging cellular functions. These discoveries were largely linked to Cx43, which is prominent in most human organs. Here, we will review the evolution of knowledge on connexin expression in human adults and more recent evidence linking connexins to a highly diverse array of cellular functions.
摘要：
超过35年前，细胞生物群落被引入连接蛋白，作为用于组装细胞间通道的半结晶簇的亚基，这些细胞间通道在形态上已被很好地描述为间隙连接。在接下来的十年中，人们对出乎意料的21个成员组成的人类连接蛋白家族的了解不断增长，以反映所有器官系统中独特而重叠的表达模式。虽然连接蛋白生物学最初专注于它们在构建高度调节的细胞间通道中的作用，这注定要改变，因为发现细胞表面的连接蛋白半通道在许多细胞类型中具有新的作用，尤其是在考虑连接蛋白病理时。连接蛋白具有双功能通道特性的接受最初遇到了一些阻力，近年来，这已经被连接蛋白具有多功能特性的前提所取代。根据连接蛋白的同工型和起源细胞，连接蛋白具有广泛的半衰期，从几个小时到细胞的预期寿命不等。通过X射线晶体学和单粒子低温电子显微镜进一步揭示了连接蛋白通道特征和分子特性的多样性。新的途径已经看到连接蛋白或连接蛋白片段在细胞粘附中起作用，隧穿纳米管,细胞外囊泡，线粒体膜，转录调节，以及其他新兴的细胞功能。这些发现在很大程度上与Cx43有关，Cx43在大多数人体器官中很突出。这里,我们将回顾人类成人中关于连接蛋白表达的知识的演变，以及最近的证据，将连接蛋白与高度多样化的细胞功能联系起来，这些功能远远超出了它们在细胞间通讯中组装导管的最典型作用。
