title: Remote control of A-band cardiac thin filaments by the I-Z-I protein network of cardiac sarcomeres.
abstract: A conventional view of the role of sarcomeric thin filaments in cardiac function is that they react with cross-bridges that translate them toward the center of the sarcomere in a reaction triggered by Ca(2+) and powered by ATP. However, thin filaments also engage in a complex network of protein-protein interactions in the Z-disc. Thus, in the modern context, understanding of what thin filaments do in the heart must take into account not only A-band regions that react with cross-bridges, but also I-Z-I regions that rarely, if ever, react with cross-bridges and dwell near and within the Z-disc. To highlight these multiplex functions of the thin filament, I discuss the hypothesis that physical and chemical reactions at the interface of the thin filaments with Z-disc proteins control the docking and activity of kinases and phosphatases that control the levels of phosphorylation of thin filament regulatory proteins. Testing this hypothesis has taken on new significance with the identification of multisite phosphorylation of thin filament proteins as a critical element in the control of cardiac contraction and relaxation reserve and in maladaptive mechanisms in heart failure. Moreover, multiple mutations in Z-disc proteins that link to prevalent cardiomyopathies are likely to alter this remote control of A-band thin filament function.
authors.affiliation: Department of Physiology and Biophysics and Center for Cardiovascular Research, College of Medicine, University of Illinois at Chicago, 835 S. Wolcott Avenue, Chicago, IL 60612, USA. solarorj@uic.edu
authors.forename: R John
authors.initials: RJ
authors.lastname: Solaro
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D000818:Animals; D006321:Heart / Q000502:physiology*; D006801:Humans; D009124:Muscle Proteins / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D012518:Sarcomeres / Q000378:metabolism*
chemical_list: D009124:Muscle Proteins