Muscle specific stress fibers give rise to sarcomeres in cardiomyocytes

  1. Aidan M Fenix
  2. Abigail C Neininger
  3. Nilay Taneja
  4. Karren Hyde
  5. Mike R Visetsouk
  6. Ryan J Garde
  7. Baohong Liu
  8. Benjamin R Nixon
  9. Annabelle E Manalo
  10. Jason R Becker
  11. Scott W Crawley
  12. David Mansfield bader
  13. Matthew J Tyska
  14. Qi Liu
  15. Jennifer H Gutzman
  16. Dylan Tyler Burnette  Is a corresponding author
  1. Vanderbilt University, United States
  2. University of Wisconsin, Milwaukee, United States
  3. Vanderbilt University Medical Center, United States
  4. 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.

The following data sets were generated

Article and author information

Author details

  1. Aidan M Fenix

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Abigail C Neininger

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Nilay Taneja

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Karren Hyde

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Mike R Visetsouk

    Department of Biological Sciences, University of Wisconsin, Milwaukee, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Ryan J Garde

    Department of Biological Sciences, University of Wisconsin, Milwaukee, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Baohong Liu

    Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Benjamin R Nixon

    Department of Medicine, Vanderbilt University Medical Center, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1840-0179
  9. Annabelle E Manalo

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Jason R Becker

    Department of Medicine, Vanderbilt University Medical Center, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2107-8179
  11. Scott W Crawley

    Department of Biological Sciences, University of Toledo, Toledo, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. David Mansfield bader

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Matthew J Tyska

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Qi Liu

    Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Jennifer H Gutzman

    Department of Biological Sciences, University of Wisconsin, Milwaukee, Milwaukee, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7725-6923
  16. Dylan Tyler Burnette

    Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States
    For correspondence
    dylan.burnette@vanderbilt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2571-7038

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.

Reviewing Editor

  1. Anna Akhmanova, Utrecht University, Netherlands

Version history

  1. Received: September 18, 2018
  2. Accepted: December 11, 2018
  3. Accepted Manuscript published: December 12, 2018 (version 1)
  4. Version of Record published: December 27, 2018 (version 2)

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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  1. Aidan M Fenix
  2. Abigail C Neininger
  3. Nilay Taneja
  4. Karren Hyde
  5. Mike R Visetsouk
  6. Ryan J Garde
  7. Baohong Liu
  8. Benjamin R Nixon
  9. Annabelle E Manalo
  10. Jason R Becker
  11. Scott W Crawley
  12. David Mansfield bader
  13. Matthew J Tyska
  14. Qi Liu
  15. Jennifer H Gutzman
  16. Dylan Tyler Burnette
(2018)
Muscle specific stress fibers give rise to sarcomeres in cardiomyocytes
eLife 7:e42144.
https://doi.org/10.7554/eLife.42144

Share this article

https://doi.org/10.7554/eLife.42144

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