Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila

  1. Hannah J Green
  2. Annabel G M Griffiths
  3. Jari Ylänne
  4. Nicholas H Brown  Is a corresponding author
  1. University of Cambridge, United Kingdom
  2. University of Jyväskylä, Finland

Abstract

We use the myotendinous junction of Drosophila flight muscles to explore why many integrin associated proteins (IAPs) are needed and how their function is coordinated. These muscles revealed new functions for IAPs not required for viability: Focal Adhesion Kinase (FAK), RSU1, tensin and vinculin. Genetic interactions demonstrated a balance between positive and negative activities, with vinculin and tensin positively regulating adhesion, while FAK inhibits elevation of integrin activity by tensin, and RSU1 keeps PINCH activity in check. The molecular composition of myofibril termini resolves into 4 distinct layers, one of which is built by a mechanotransduction cascade: vinculin facilitates mechanical opening of filamin, which works with the Arp2/3 activator WASH to build an actin-rich layer positioned between integrins and the first sarcomere. Thus, integration of IAP activity is needed to build the complex architecture of the myotendinous junction, linking the membrane anchor to the sarcomere.

Data availability

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

Article and author information

Author details

  1. Hannah J Green

    Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3039-3015
  2. Annabel G M Griffiths

    Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Jari Ylänne

    Department of Biological and Environmental Sciences, University of Jyväskylä, Jyväskylä, Finland
    Competing interests
    The authors declare that no competing interests exist.
  4. Nicholas H Brown

    Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    nb117@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8958-7017

Funding

Wellcome (099739/Z/12/Z)

  • Hannah J Green

Medical Research Council

  • Annabel G M Griffiths

Biotechnology and Biological Sciences Research Council (BB/L006669/1)

  • Nicholas H Brown

Suomen Akatemia (278668)

  • Hannah J Green

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, Max Planck Institute of Biochemistry, Germany

Publication history

  1. Received: February 9, 2018
  2. Accepted: July 19, 2018
  3. Accepted Manuscript published: July 20, 2018 (version 1)
  4. Version of Record published: August 14, 2018 (version 2)

Copyright

© 2018, Green 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. Hannah J Green
  2. Annabel G M Griffiths
  3. Jari Ylänne
  4. Nicholas H Brown
(2018)
Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila
eLife 7:e35783.
https://doi.org/10.7554/eLife.35783
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