title: Cardiomyocyte cytoskeleton and myofibrillogenesis in healthy and diseased heart.
abstract: The unique cytoarchitecture of cardiomyocytes arises by complex interactions of different filamentous structures of the cytoskeleton. Intermediate filaments of the non-sarcomeric cytoskeleton are not essential for development but important for maintenance of myofibrils. Myofibrils consist of contractile proteins involved in force generation and the muscle cytoskeleton framework. The latter is essential for proper assembly and maintenance as well as for interaction with other cardiomyocytes or the extracellular matrix, thus being involved in force transmission. The information for sarcomere assembly is encoded in the proteins and some domains essential for faithful incorporation have been identified by epitope tagging experiments. Many KO mutations result in embryonic lethal phenotypes and new techniques e.g. using cardiomyocytes derived from ES cell-lines will have to be developed that allow to study such mutations in cardiomyocytes rather than whole organisms. Alterations in the expression levels of several proteins of the muscle cytoskeleton or impairment of their function by point mutations can result in increased mechanical stress in the cardiomyocytes which finally leads to cellular responses such as the development of dilated cardiomyopathy (DCM). MLP (muscle-LIM-protein) deficient mice develop DCM and changes in the mechanical coupling of cardiomyocytes result in alterations at the intercalated disks and enhanced accumulation of adherens junction proteins. Therefore, controlled interactions between proteins of the muscle cytoskeleton and contractile proteins are essential to ensure proper cardiac function and a more detailed insight in these processes might provide new tools to improve the contractile efficiency of the cardiomyocytes and thus working output in cardiomyopathies.
authors.affiliation: Institute of Cell Biology ETH, Swiss Federal Institute of Technology, CH-8093, Zürich, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Ehler
authors.forename: J C
authors.initials: JC
authors.lastname: Perriard
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D003285:Contractile Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D024510:Muscle Development / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology / Q000648:ultrastructure*; D051381:Rats; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D003285:Contractile Proteins; D008840:Microfilament Proteins; D049452:Green Fluorescent Proteins