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Muscle specific stress fibers give rise to sarcomeres in cardiomyocytes


Fenix AM , Neininger AC , Taneja N , Hyde K , Visetsouk MR , Garde RJ , Liu B , Nixon BR , Manalo AE , Becker JR , Crawley SW , Bader DM , Tyska MJ , Liu Q , Gutzman JH , Burnette DT , . eLife. 2018 12 12; 7().


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 ┬Ám 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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