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Muscle specific stress fibers give rise to sarcomeres in cardiomyocytes

Authors

Fenix AM Aidan M , Neininger AC Abigail C , Taneja N Nilay , Hyde K Karren , Visetsouk MR Mike R , Garde RJ Ryan J , Liu B Baohong , Nixon BR Benjamin R , Manalo AE Annabelle E , Becker JR Jason R , Crawley SW Scott W , Bader DM David Mansfield , Tyska MJ Matthew J , Liu Q Qi , Gutzman JH Jennifer H , Burnette DT Dylan Tyler .
eLife. 2018 12 12; 7().

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.

Tags: Publications, Student Publications