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 7

PMID: 30540249 · PMCID: PMC6307863 · DOI:10.7554/eLife.42144

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.

© 2018, Fenix et al.

MeSH Terms (16)

Actin Cytoskeleton Actins Cell Line Cell Line, Tumor HeLa Cells Humans Microfilament Proteins Microscopy, Confocal Molecular Motor Proteins Muscle Fibers, Skeletal Myocytes, Cardiac Myosin Heavy Chains Nonmuscle Myosin Type IIB RNA Interference Sarcomeres Stress Fibers

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