Derbala Mohamed H, Guo Aaron S, Mohler Peter J, Smith Sakima A
Dorothy M. Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
Dorothy M. Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH, USA.
Life Sci. 2018 Jan 1;192:278-285. doi: 10.1016/j.lfs.2017.11.009. Epub 2017 Nov 9.
Spectrins are large, flexible proteins comprised of α-β dimers that are connected head-to-head to form the canonical heterotetrameric spectrin structure. Spectrins were initially believed to be exclusively found in human erythrocytic membrane and are highly conserved among different species. βII spectrin, the most common isoform of non-erythrocytic spectrin, is found in all nucleated cells and forms larger macromolecular complexes with ankyrins and actins. Not only is βII spectrin a central cytoskeletal scaffolding protein involved in preserving cell structure but it has also emerged as a critical protein required for distinct physiologic functions such as posttranslational localization of crucial membrane proteins and signal transduction. In the heart, βII spectrin plays a vital role in maintaining normal cardiac membrane excitability and proper cardiac development during embryogenesis. Mutations in βII spectrin genes have been strongly linked with the development of serious cardiac disorders such as congenital arrhythmias, heart failure, and possibly sudden cardiac death. This review focuses on our current knowledge of the role βII spectrin plays in the cardiovascular system in health and disease and the potential future clinical implications.
血影蛋白是由α-β二聚体组成的大型柔性蛋白，这些二聚体头对头连接形成典型的异源四聚体血影蛋白结构。血影蛋白最初被认为仅存在于人类红细胞膜中，并且在不同物种间高度保守。βII血影蛋白是非红细胞血影蛋白最常见的亚型，存在于所有有核细胞中，并与锚蛋白和肌动蛋白形成更大的大分子复合物。βII血影蛋白不仅是一种参与维持细胞结构的核心细胞骨架支架蛋白，还已成为不同生理功能（如关键膜蛋白的翻译后定位和信号转导）所需的关键蛋白。在心脏中，βII血影蛋白在维持正常心脏膜兴奋性和胚胎发育期间的正常心脏发育中起着至关重要的作用。βII血影蛋白基因突变与严重心脏疾病（如先天性心律失常、心力衰竭以及可能的心脏性猝死）的发生密切相关。本综述聚焦于我们目前对βII血影蛋白在健康和疾病状态下心血管系统中所起作用的认识以及未来潜在的临床意义。
