Protein Phosphorylation and Signal Transduction in Cardiac Thin Filaments

Homeostasis of cardiac function requires significant adjustments in sarcomeric protein phosphorylation. The existence of unique peptides in cardiac sarcomeres, which are substrates for a multitude of kinases, strongly supports this concept (1). We focus here on the troponin complex of the thin filaments, which contain two major proteins that participate in these phosphoryl group transfer reactions: the inhibitory protein (cardiac troponin (cTn)(2) I) and the tropomyosin (Tm)-binding protein (cTnT). We describe the relatively new understanding of the molecular mechanisms of thin filament-based control of the heartbeat and how these mechanisms are altered by phosphorylation. We discuss new concepts regarding the relation between the beat of the heart and the location of thin filament proteins and their long-and short-range interactions. We also discuss elucidation of mechanisms by which these phosphorylations exacerbate or ameliorate effects of mutations in the myofilament proteins that are linked to familial cardiomyopathies.