Tropomyosin de-phosphorylation in the heart: what are the consequences?

The focus of this review is on the very recent work we have conducted that addresses the molecular, morphological, and physiological significance of cardiac tropomyosin phosphorylation in the heart. We employ transgenic mice to address questions of how cardiomyocytes and the whole heart respond when the tropomyosin phosphorylation site (Ser283) is converted to a non-phosphorylatable amino acid (Ala). We address the phenotype of these mice during normal development and in response to acute cardiac stress (transaortic coarctation). In addition, we also examined how transgenic mice encoding the altered tropomyosin phosphorylation site (Ser283Ala) would respond to chronic cardiac stress through an encoded hypertrophic cardiomyopathy mutation (Glu180Gly). These studies are the first to address the in vivo significance of tropomyosin phosphorylation in the heart. In this review manuscript, we report the recent findings of these investigations.