Jung Paul, Fiedelak André, Dreeßen Celina, Huber Otmar, Reiche Juliane
Institute of Biochemistry II, Jena University Hospital, Friedrich Schiller University Jena, Nonnenplan 2-4, 07743 Jena, Germany.
Cells. 2024 Dec 6;13(23):2018. doi: 10.3390/cells13232018.
There is no doubt that the proper development of the heart is important for its correct function, in addition, maturation processes of the heart are crucial as well. The actin-binding protein nexilin seems to take over central roles in the latter processes, as nexilin-deficient mice are phenotypically inconspicuous at birth but die within short time thereafter. Recently, it has been proposed that nexilin plays a role in the formation and function of transverse tubules (T-tubules), which are essential for excitation-contraction coupling in the hearts of mature animals. Although it has long been known that nexilin is subjected to alternative splicing, a molecular characterization of the respective isoforms is not yet available. Here, we describe novel nexilin splice variants and analyze their expression in tissues of mice and humans. Interestingly, nexilin isoforms segregate to myocyte- and epithelial-specific isoforms. Moreover, heart-specific isoforms of nexilin localize differently between atria and ventricles and are also expressed in the endothelial cells of blood vessels. Further, we narrowed down the critical exons in the actin-binding domains 1 and 2 (ABD1/2), and observed different self-interaction properties by recombinant protein interaction studies. Our results emphasize the diverse tissue and subcellular distribution of the individual nexilin isoforms and point to the importance of taking a closer look at the particular nexilin isoforms investigated.
毫无疑问，心脏的正常发育对其正常功能很重要，此外，心脏的成熟过程也至关重要。肌动蛋白结合蛋白纽带蛋白似乎在后一过程中发挥核心作用，因为缺乏纽带蛋白的小鼠出生时表型不明显，但此后不久就会死亡。最近，有人提出纽带蛋白在横管（T管）的形成和功能中起作用，而横管对成熟动物心脏的兴奋-收缩偶联至关重要。尽管人们早就知道纽带蛋白存在可变剪接，但尚未对各自的异构体进行分子表征。在这里，我们描述了新型纽带蛋白剪接变体，并分析了它们在小鼠和人类组织中的表达。有趣的是，纽带蛋白异构体分为心肌细胞特异性和上皮细胞特异性异构体。此外，心脏特异性纽带蛋白异构体在心房和心室之间的定位不同，并且也在血管内皮细胞中表达。此外，我们缩小了肌动蛋白结合结构域1和2（ABD1/2）中的关键外显子范围，并通过重组蛋白相互作用研究观察到了不同的自我相互作用特性。我们的结果强调了各个纽带蛋白异构体在组织和亚细胞水平上的不同分布，并指出仔细研究特定的纽带蛋白异构体的重要性。
