Complexity in simplicity: monogenic disorders and complex cardiomyopathies

作者：Ju Chen, Kenneth R. Chien · 发表于：Journal of Clinical Investigation · 年份：1999 · DOI：10.1172/jci7297 · 被引用次数：87 · 研究领域：Cardiomyopathy and Myosin Studies、Cardiovascular Effects of Exercise、Muscle Physiology and Disorders

nents of the primary cardiac cytoarchitecture, including components of the cardiac contractile sarcomere, and the intrasarcomeric, and extrasarcomeric cytoskeleton (2, 3, 7). The cytosol of all eukaryotic cells contains a network of protein filaments and associated proteins which collectively constitute the cytoskeleton. Among these filaments are the actin microfilaments, the somewhat wider tubulin microtubules, and the intermediate filaments. To perform force-generating contraction, and to accommodate the repetitive changes in cell geometry that occur during each cardiac cycle, cardiac myocytes have evolved an abundant and highly specialized cytoskeleton, whose components can be classified into the following 3 groups: (a) The force-generating contractile sarcomeric cytoskeleton consists of a highly-ordered arrangement of myosin thick filaments, actin thin filaments, and associated proteins, such as the troponin‐tropomyosin complex. The repeating sarcomere units are arranged in series, resulting in striated myofibrils. (b) The intrasarcomeric cytoskeleton contains titin, α-actinin, myosin binding protein C, and other proteins that anchor myofilaments and their sarcomeric units and regulate the displacement of myofilaments during each contraction cycle. (c) The extrasarcomeric cytoskeleton is composed of desmin and lamin-containing intermediate filaments that provide a link between adjacent myofibrils and a framework for the nuclear envelope. This extrasarcomeric network also ...