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. Ge...
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Format: | Article |
Language: | English |
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eLife Sciences Publications Ltd
2018-07-01
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Series: | eLife |
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Online Access: | https://elifesciences.org/articles/35783 |
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author | Hannah J Green Annabel GM Griffiths Jari Ylänne Nicholas H Brown |
author_facet | Hannah J Green Annabel GM Griffiths Jari Ylänne Nicholas H Brown |
author_sort | Hannah J Green |
collection | DOAJ |
description | 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. |
first_indexed | 2024-04-12T16:46:04Z |
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id | doaj.art-5edfa5ed952d4fd0a26c96f176caef12 |
institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-12T16:46:04Z |
publishDate | 2018-07-01 |
publisher | eLife Sciences Publications Ltd |
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series | eLife |
spelling | doaj.art-5edfa5ed952d4fd0a26c96f176caef122022-12-22T03:24:34ZengeLife Sciences Publications LtdeLife2050-084X2018-07-01710.7554/eLife.35783Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in DrosophilaHannah J Green0https://orcid.org/0000-0002-3039-3015Annabel GM Griffiths1Jari Ylänne2https://orcid.org/0000-0003-4627-021XNicholas H Brown3https://orcid.org/0000-0002-8958-7017Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom; Department of Biological and Environmental Sciences, University of Jyväskylä, Jyväskylä, Finland; Nanoscience Center, University of Jyväskylä, Jyväskylä, FinlandDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomDepartment of Biological and Environmental Sciences, University of Jyväskylä, Jyväskylä, Finland; Nanoscience Center, University of Jyväskylä, Jyväskylä, FinlandDepartment of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United KingdomWe 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.https://elifesciences.org/articles/35783cell-ECM adhesionmyotendinous junctionactin cytoskeletonintegrinvinculinfilamin |
spellingShingle | Hannah J Green Annabel GM Griffiths Jari Ylänne Nicholas H Brown Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila eLife cell-ECM adhesion myotendinous junction actin cytoskeleton integrin vinculin filamin |
title | Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila |
title_full | Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila |
title_fullStr | Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila |
title_full_unstemmed | Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila |
title_short | Novel functions for integrin-associated proteins revealed by analysis of myofibril attachment in Drosophila |
title_sort | novel functions for integrin associated proteins revealed by analysis of myofibril attachment in drosophila |
topic | cell-ECM adhesion myotendinous junction actin cytoskeleton integrin vinculin filamin |
url | https://elifesciences.org/articles/35783 |
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