The neglected messengers: Control of cardiac myofilaments by protein phosphatases

•Control of cardiac myofilament function by protein phosphatases is largely neglected.•Serine-threonine protein phosphatases target multiple myofilament proteins.•Myofilament protein dephosphorylation has significant functional impact.•Discrepancies due to isoforms, compartmentalization, and complex signaling cascades•Myofilament protein phosphatases important in heart failure

Cardiac myofilaments act as the central contractile apparatus of heart muscle cells. Covalent modification of constituent proteins through phosphorylation is a rapid and powerful mechanism to control myofilament function, and is increasingly seen as a mechanism of disease. While the relationship between protein kinases and cardiac myofilaments has been widely examined, the impact of protein dephosphorylation by protein phosphatases is poorly understood. This review outlines the mechanisms by which the mostly widely expressed protein phosphatases in cardiac myocytes regulate myofilament function, and the emerging role of myofilament-associated protein phosphatases in heart failure. The importance of regulatory subunits and subcellular compartmentalization in determining the functional impact of protein phosphatases on myofilament and myocardial function is also discussed, as are discrepancies about the roles of protein phosphatases in regulating myofilament function. The potential for targeting these molecular messengers in the treatment of heart failure is discussed as a key future direction.