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...

Full description

Bibliographic Details
Main Authors: Hannah J Green, Annabel GM Griffiths, Jari Ylänne, Nicholas H Brown
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-07-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/35783
_version_ 1811253133607698432
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
format Article
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
record_format Article
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
work_keys_str_mv AT hannahjgreen novelfunctionsforintegrinassociatedproteinsrevealedbyanalysisofmyofibrilattachmentindrosophila
AT annabelgmgriffiths novelfunctionsforintegrinassociatedproteinsrevealedbyanalysisofmyofibrilattachmentindrosophila
AT jariylanne novelfunctionsforintegrinassociatedproteinsrevealedbyanalysisofmyofibrilattachmentindrosophila
AT nicholashbrown novelfunctionsforintegrinassociatedproteinsrevealedbyanalysisofmyofibrilattachmentindrosophila