Abstract

Myofibrils are huge cytoskeletal assemblies embedded in the cytosol of muscle cells. They consist of arrays of sarcomeres, the smallest contractile unit of muscles. Within a muscle type, myofibril diameter is highly invariant and contributes to its physiological properties, yet little is known about the underlying mechanisms setting myofibril diameter. Here we show that the PDZ and LIM domain protein Zasp, a structural component of Z-discs, mediates Z-disc and thereby myofibril growth through protein oligomerization. Oligomerization is induced by an interaction of its ZM domain with LIM domains. Oligomerization is terminated upon upregulation of shorter Zasp isoforms which lack LIM domains at later developmental stages. The balance between these two isoforms, which we call growing and blocking isoforms sets the stereotyped diameter of myofibrils. If blocking isoforms dominate, myofibrils become smaller. If growing isoforms dominate, myofibrils and Z-discs enlarge, eventually resulting in large pathological aggregates that disrupt muscle function.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

The following previously published data sets were used

Article and author information

Author details

  1. Nicanor González-Morales

    Department of Biology, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1305-8992
  2. Yu Shu Xiao

    Department of Biology, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Matthew Aaron Schilling

    Department of Biology, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  4. Océane Marescal

    Department of Biology, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  5. Kuo An Liao

    Department of Biology, McGill University, Montreal, Canada
    Competing interests
    The authors declare that no competing interests exist.
  6. Frieder Schöck

    Department of Biology, McGill University, Montreal, Canada
    For correspondence
    frieder.schoeck@mcgill.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1351-0574

Funding

Canadian Institutes of Health Research (MOP-142475)

  • Nicanor González-Morales
  • Yu Shu Xiao
  • Matthew Aaron Schilling
  • Océane Marescal
  • Kuo An Liao

Canadian Institutes of Health Research (PJT-155995)

  • Nicanor González-Morales
  • Yu Shu Xiao
  • Matthew Aaron Schilling
  • Océane Marescal
  • Kuo An Liao

Natural Sciences and Engineering Research Council of Canada (RGPIN 2016-06793)

  • Nicanor González-Morales
  • Yu Shu Xiao
  • Matthew Aaron Schilling
  • Océane Marescal
  • Kuo An Liao

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Frank Schnorrer, Aix Marseille University, France

Version history

  1. Received: July 24, 2019
  2. Accepted: November 18, 2019
  3. Accepted Manuscript published: November 20, 2019 (version 1)
  4. Version of Record published: December 13, 2019 (version 2)
  5. Version of Record updated: December 16, 2019 (version 3)

Copyright

© 2019, González-Morales 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. Nicanor González-Morales
  2. Yu Shu Xiao
  3. Matthew Aaron Schilling
  4. Océane Marescal
  5. Kuo An Liao
  6. Frieder Schöck
(2019)
Myofibril diameter is set by a finely tuned mechanism of protein oligomerization in Drosophila
eLife 8:e50496.
https://doi.org/10.7554/eLife.50496

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https://doi.org/10.7554/eLife.50496

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