The Role of Tropomyosin in Cardiac Function and Disease

Abstract

Phosphorylation of cardiac sarcomeric proteins plays a major role in the regulation of physiological performance of the heart. Tropomyosin, an essential thin filament protein, regulates muscle contraction and relaxation through its interactions with actin, myosin, and the troponin complex. Studies demonstrate that changes in tropomyosin phosphorylation occur both postpartum and in response to cardiac hypertrophy and heart failure. To address the significance of tropomyosin phosphorylation on cardiac function, we conducted experiments to ascertain the effects of constitutive pseudophosphorylation, dephosphorylation, and dephosphorylation in hypertrophic cardiomyopathic hearts. Recent work demonstrates that pseudophosphorylation of tropomyosin results in dilated cardiomyopathy. Tropomyosin dephosphorylation results in a compensated or physiological cardiac hypertrophic phenotype. In addition, we demonstrated that tropomyosin dephosphorylation phenotypically rescues hearts undergoing cardiac hypertrophy. In summary, these studies collectively demonstrate a significant biological and physiological role for tropomyosin phosphorylation under both normal and cardiomyopathic conditions.