The role of βII spectrin in cardiac health and disease

Spectrins are large, flexible proteins comprised of alpha-beta 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. beta II 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 beta II 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, beta II spectrin plays a vital role in maintaining normal cardiac membrane excitability and proper cardiac development during embryogenesis. Mutations in beta II 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 beta II spectrin plays in the cardiovascular system in health and disease and the potential future clinical implications.