Muscle-specific stress fibers give rise to sarcomeres in cardiomyocytes
Sarcomeres
0301 basic medicine
QH301-705.5
Science
Muscle Fibers, Skeletal
Formins
cardiomyocytes
myosin
7. Clean energy
sarcomeres
Cell Line
03 medical and health sciences
Cell Line, Tumor
Stress Fibers
Humans
Myocytes, Cardiac
Biology (General)
Microscopy, Confocal
Nonmuscle Myosin Type IIB
Myosin Heavy Chains
Molecular Motor Proteins
Q
Microfilament Proteins
R
Cell Biology
Actins
formins
Actin Cytoskeleton
13. Climate action
Medicine
RNA Interference
actin
HeLa Cells
DOI:
10.7554/elife.42144
Publication Date:
2018-12-12T13:01:35Z
AUTHORS (16)
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.
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