Muscle specific stress fibers give rise to sarcomeres in cardiomyocytes
- Vanderbilt University, United States
- University of Wisconsin, Milwaukee, United States
- Vanderbilt University Medical Center, United States
- University of Toledo, United States
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.
Data availability
Sequencing data have been deposited in GEO under accession codes GSE119743. All other data generated or analysed during this study are included in the manuscript and supporting files.
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Cardiomyocyte mRNA ContentNCBI Gene Expression Omnibus, GSE119743.
Article and author information
Author details
Jennifer H Gutzman
Dylan Tyler Burnette
Funding
National Institute of General Medical Sciences (R35 GM125028)
- Dylan Tyler Burnette
National Heart, Lung, and Blood Institute (F31 HL136081)
- Aidan M Fenix
American Heart Association (16PRE29100014)
- Aidan M Fenix
National Cancer Institute (P50 CA095103)
- Dylan Tyler Burnette
American Heart Association (17SDG33460353)
- Dylan Tyler Burnette
National Heart, Lung, and Blood Institute (RO1 HL037675)
- David Mansfield bader
National Heart, Lung, and Blood Institute (K08 HL116803)
- Jason R Becker
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Fenix et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Muscle specific stress fibers give rise to sarcomeres in cardiomyocytes
eLife 7:e42144.
https://doi.org/10.7554/eLife.42144
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