Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila
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.
All data generated or analysed during this study are included in the manuscript and supporting files
Article and author information
- 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.
- Frank Schnorrer, Max Planck Institute of Biochemistry, Germany
- Received: February 9, 2018
- Accepted: July 19, 2018
- Accepted Manuscript published: July 20, 2018 (version 1)
- Version of Record published: August 14, 2018 (version 2)
© 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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