Muscle-specific stress fibers give rise to sarcomeres in cardiomyocytes

Sarcomeres 0301 basic medicine QH301-705.5 Science Muscle Fibers, Skeletal Formins cardiomyocytes myosin 7. Clean energy sarcomeres Cell Line 03 medical and health sciences Cell Line, Tumor Stress Fibers Humans Myocytes, Cardiac Biology (General) Microscopy, Confocal Nonmuscle Myosin Type IIB Myosin Heavy Chains Molecular Motor Proteins Q Microfilament Proteins R Cell Biology Actins formins Actin Cytoskeleton 13. Climate action Medicine RNA Interference actin HeLa Cells
DOI: 10.7554/elife.42144 Publication Date: 2018-12-12T13:01:35Z
ABSTRACT
The sarcomere is the contractile unit within cardiomyocytes driving heart muscle contraction. We sought to test the mechanisms regulating actin and myosin filament assembly during sarcomere formation. Therefore, we developed an assay using human cardiomyocytes to monitor sarcomere assembly. We report a population of muscle stress fibers, similar to actin arcs in non-muscle cells, which are essential sarcomere precursors. We show sarcomeric actin filaments arise directly from muscle stress fibers. This requires formins (e.g., FHOD3), non-muscle myosin IIA and non-muscle myosin IIB. Furthermore, we show short cardiac myosin II filaments grow to form ~1.5 μm long filaments that then ‘stitch’ together to form the stack of filaments at the core of the sarcomere (i.e., the A-band). A-band assembly is dependent on the proper organization of actin filaments and, as such, is also dependent on FHOD3 and myosin IIB. We use this experimental paradigm to present evidence for a unifying model of sarcomere assembly.
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