Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States.
Department of Biological Sciences, Cell and Molecular Biology, University of Wisconsin Milwaukee, Milwaukee, United States.
Elife. 2018 Dec 12;7:e42144. 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.
肌节是驱动心肌收缩的心肌细胞的收缩单位。我们试图测试调节肌节形成过程中肌动蛋白和肌球蛋白丝组装的机制。因此，我们开发了一种使用人心肌细胞监测肌节组装的测定法。我们报告了一种类似于非肌肉细胞中肌动蛋白弧的肌节前体的肌节肌原纤维。我们显示肌节肌动蛋白丝直接从肌节肌原纤维产生。这需要形成蛋白（例如 FHOD3）、非肌肉肌球蛋白 IIA 和非肌肉肌球蛋白 IIB。此外，我们还表明，短的心肌肌球蛋白丝生长形成约 1.5 μm 长的丝，然后“缝合”在一起，形成肌节核心的丝堆栈（即 A 带）。A 带组装依赖于肌动蛋白丝的正确排列，因此也依赖于 FHOD3 和肌球蛋白 IIB。我们使用这种实验范例来提出肌节组装的统一模型的证据。
