1. Cell Biology
Download icon

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
Research Article
  • Cited 18
  • Views 5,178
  • Annotations
Cite this article as: eLife 2018;7:e42144 doi: 10.7554/eLife.42144
Voice your concerns about research culture and research communication: Have your say in our 7th annual survey.

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

Publication 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.

Metrics

  • 5,178
    Page views
  • 569
    Downloads
  • 18
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Cell Biology
    2. Structural Biology and Molecular Biophysics
    Agata Szuba et al.
    Research Article Updated

    Septins are conserved cytoskeletal proteins that regulate cell cortex mechanics. The mechanisms of their interactions with the plasma membrane remain poorly understood. Here, we show by cell-free reconstitution that binding to flat lipid membranes requires electrostatic interactions of septins with anionic lipids and promotes the ordered self-assembly of fly septins into filamentous meshworks. Transmission electron microscopy reveals that both fly and mammalian septin hexamers form arrays of single and paired filaments. Atomic force microscopy and quartz crystal microbalance demonstrate that the fly filaments form mechanically rigid, 12- to 18-nm thick, double layers of septins. By contrast, C-terminally truncated septin mutants form 4-nm thin monolayers, indicating that stacking requires the C-terminal coiled coils on DSep2 and Pnut subunits. Our work shows that membrane binding is required for fly septins to form ordered arrays of single and paired filaments and provides new insights into the mechanisms by which septins may regulate cell surface mechanics.

    1. Cell Biology
    Na Li et al.
    Research Article Updated

    Adiponectin is essential for the regulation of tissue substrate utilization and systemic insulin sensitivity. Clinical studies have suggested a positive association of circulating adiponectin with healthspan and lifespan. However, the direct effects of adiponectin on promoting healthspan and lifespan remain unexplored. Here, we are using an adiponectin null mouse and a transgenic adiponectin overexpression model. We directly assessed the effects of circulating adiponectin on the aging process and found that adiponectin null mice display exacerbated age-related glucose and lipid metabolism disorders. Moreover, adiponectin null mice have a significantly shortened lifespan on both chow and high-fat diet. In contrast, a transgenic mouse model with elevated circulating adiponectin levels has a dramatically improved systemic insulin sensitivity, reduced age-related tissue inflammation and fibrosis, and a prolonged healthspan and median lifespan. These results support a role of adiponectin as an essential regulator for healthspan and lifespan.