title: The neglected messengers: Control of cardiac myofilaments by protein phosphatases.
abstract: 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.
authors.affiliation: Centre for Cardiovascular Investigations, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.
authors.forename: Ilka
authors.initials: I
authors.lastname: Lorenzen-Schmidt
authors.affiliation: Centre for Cardiovascular Investigations, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.
authors.forename: Samantha B
authors.initials: SB
authors.lastname: Clarke
authors.affiliation: Centre for Cardiovascular Investigations, Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada. Electronic address: gpyle@uoguelph.ca.
authors.forename: W Glen
authors.initials: WG
authors.lastname: Pyle
mesh_terms: D000818:Animals; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D007527:Isoenzymes; D008840:Microfilament Proteins; D010749:Phosphoprotein Phosphatases
keywords: Heart failure; Myofilaments; Protein phosphatases