Cx43截短型异构体相关研究综述
A Review of Research on Truncated Isoforms of Cx43
DOI: 10.12677/acm.2026.1693026, PDF,   
作者: 鲍昱帆, 刘月华, 赵 丽*：中国药科大学基础医学与临床药学学院，江苏 南京
关键词: 连接蛋白；Cx43；异构体；GJA1-20k；GJA1-11k；Connexin； Cx43； Isoforms； GJA1-20k； GJA1-11k
摘要: 连接蛋白(Connexin)，是一类能够形成间隙连接的膜蛋白，对细胞间通讯非常重要。Connexin 43 (Cx43)，由GJA1编码，是表达最为丰富的蛋白，尤其是在心脏中。基于Cx43的间隙连接能够实现离子在细胞间的直接转运，从而协调心肌细胞之间的电信号，在维持心律的过程中发挥重要的作用。Cx43的表达和定位的改变已被证实与心源性猝死和心力衰竭等多种病理过程有关。C43能够通过GJA1 mRNA的内部翻译形成多种异构体，这对Cx43的功能非常重要。越来越多的证据表明，在这些异构体中表达最为丰富的GJA1-20k，能够发挥细胞通讯以外的功能，包括维持线粒体稳态，保护细胞免受氧化应激，调节线粒体预适应，以及调节细胞骨架等。GJA1-20k在这些过程中的作用，使得它具有巨大的治疗潜力，特别是在治疗心肌梗死、缺血/再灌注损伤和心律失常等心血管疾病方面。除了GJA1-20k，GJA1-11k也被发现具有和全长Cx43不一样的独特作用。了解GJA1-11k的生成以及它在细胞周期中的作用，或许能够成为在多种疾病模型中调控细胞生长的新靶点。我们对这些异构体进行了总结，希望能够对Cx43和产生的异构体有更加整体全面的认识。
Abstract: Connexins are membrane proteins forming gap junctions essential for intercellular communication. Connexin 43 (Cx43), encoded by GJA1, is the most abundant connexin, especially in the heart. Cx43-based gap junctions enable the direct intercellular transport of ions, critical for cardiac rhythm by synchronizing electrical impulses between heart cells. Alterations in Cx43 expression and localization have been implicated in pathologies from sudden cardiac death to heart failure. Essential to Cx43 function is its intrinsic ability to form diverse isoforms through internal translation of GJA1 mRNA. Evidence has accumulated that, GJA1-20k, the most abundant of these isoforms, has been recognized to have a wide range of additional functions beyond directing Cx43-based intercellular communication, including maintaining mitochondrial homeostasis, protecting against oxidative stress, mediating mitochondrial preconditioning and cytoskeletal modulation. The involvement of GJA1-20k in these processes confers it great therapeutic potential, especially in treating cardiovascular diseases such as myocardial infarction, ischemia/reperfusion injuries, and arrhythmias. In addition to GJA1-20k, GJA1-11k has also been found to have unique roles different from those of full-length Cx43. Understanding the apparently unique role of GJA1-11k and its generation in cell cycle regulation may uncover a new target for affecting cell growth in multiple disease models. We have summarized these isoforms, hoping to gain a more holistic and comprehensive understanding of Cx43 and the isoforms produced.
文章引用：鲍昱帆, 刘月华, 赵丽. Cx43截短型异构体相关研究综述[J]. 临床医学进展, 2026, 16(9): 98-110. https://doi.org/10.12677/acm.2026.1693026

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