TY - JOUR TI - Muscle-specific stress fibers give rise to sarcomeres in cardiomyocytes AU - Fenix, Aidan M AU - Neininger, Abigail C AU - Taneja, Nilay AU - Hyde, Karren AU - Visetsouk, Mike R AU - Garde, Ryan J AU - Liu, Baohong AU - Nixon, Benjamin R AU - Manalo, Annabelle E AU - Becker, Jason R AU - Crawley, Scott W AU - Bader, David M AU - Tyska, Matthew J AU - Liu, Qi AU - Gutzman, Jennifer H AU - Burnette, Dylan T A2 - Akhmanova, Anna VL - 7 PY - 2018 DA - 2018/12/12 SP - e42144 C1 - eLife 2018;7:e42144 DO - 10.7554/eLife.42144 UR - https://doi.org/10.7554/eLife.42144 AB - 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. KW - cardiomyocytes KW - actin KW - myosin KW - formins KW - sarcomeres JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -