Gene regulation, alternative splicing, and posttranslational modification of troponin subunits in cardiac development and adaptation: A focused review

Abstract

Troponin plays a central role in regulating the contraction and relaxation of vertebrate striated muscles. This review focuses on the isoform gene regulation, alternative RNA splicing, and posttranslational modifications of troponin subunits in cardiac development and adaptation. Transcriptional and posttranscriptional regulations such as phosphorylation and proteolysis modifications, and structure-function relationships of troponin subunit proteins are summarized. The physiological and pathophysiological significances are discussed for impacts on cardiac muscle contractility, heart function, and adaptations in health and diseases. The primary contractile unit of striated muscles, e.g., the vertebrate cardiac and skeletal muscles, is the sarcomere. A sarcomere is comprised of overlapping myosin thick filaments and actin thin filaments. The interaction between myosin and actin activates myosin ATPase and powers myofilament sliding and muscle contraction. This process is regulated by the level of cytosolic Ca2+ through the thin filament-associated troponin-tropomyosin system (Gordon et al., 2000). Troponin plays a central role in regulating the contraction and relaxation of striated muscles. The structure and function of troponin have been extensively investigated in the past four decades as comprehensively summarized in several recent review articles (Murphy, 2006; Jin et al., 2008; Wei and Jin, 2011). To provide an overview of the current understanding of the function and regulation of troponin in cardiac muscle, the present review focuses on the isoform genes, splice-forms and posttranslational modifications of troponin in cardiac function during postnatal development and physiological and pathophysiological adaptations. © 2014 Sheng and Jin.