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Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage
Skeletal muscle expresses high levels of integrin-linked kinase (ILK), predominantly at myotendinous junctions (MTJs) and costameres. ILK binds the cytoplasmic domain of β1 integrin and mediates phosphorylation of protein kinase B (PKB)/Akt, which in turn plays a central role during skeletal muscle...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265410/ https://www.ncbi.nlm.nih.gov/pubmed/18332223 http://dx.doi.org/10.1083/jcb.200707175 |
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author | Wang, Hao-Ven Chang, Ling-Wei Brixius, Klara Wickström, Sara A. Montanez, Eloi Thievessen, Ingo Schwander, Martin Müller, Ulrich Bloch, Wilhelm Mayer, Ulrike Fässler, Reinhard |
author_facet | Wang, Hao-Ven Chang, Ling-Wei Brixius, Klara Wickström, Sara A. Montanez, Eloi Thievessen, Ingo Schwander, Martin Müller, Ulrich Bloch, Wilhelm Mayer, Ulrike Fässler, Reinhard |
author_sort | Wang, Hao-Ven |
collection | PubMed |
description | Skeletal muscle expresses high levels of integrin-linked kinase (ILK), predominantly at myotendinous junctions (MTJs) and costameres. ILK binds the cytoplasmic domain of β1 integrin and mediates phosphorylation of protein kinase B (PKB)/Akt, which in turn plays a central role during skeletal muscle regeneration. We show that mice with a skeletal muscle–restricted deletion of ILK develop a mild progressive muscular dystrophy mainly restricted to the MTJs with detachment of basement membranes and accumulation of extracellular matrix. Endurance exercise training enhances the defects at MTJs, leads to disturbed subsarcolemmal myofiber architecture, and abrogates phosphorylation of Ser473 as well as phosphorylation of Thr308 of PKB/Akt. The reduction in PKB/Akt activation is accompanied by an impaired insulin-like growth factor 1 receptor (IGF-1R) activation. Coimmunoprecipitation experiments reveal that the β1 integrin subunit is associated with the IGF-1R in muscle cells. Our data identify the β1 integrin–ILK complex as an important component of IGF-1R/insulin receptor substrate signaling to PKB/Akt during mechanical stress in skeletal muscle. |
format | Text |
id | pubmed-2265410 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-22654102008-09-10 Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage Wang, Hao-Ven Chang, Ling-Wei Brixius, Klara Wickström, Sara A. Montanez, Eloi Thievessen, Ingo Schwander, Martin Müller, Ulrich Bloch, Wilhelm Mayer, Ulrike Fässler, Reinhard J Cell Biol Research Articles Skeletal muscle expresses high levels of integrin-linked kinase (ILK), predominantly at myotendinous junctions (MTJs) and costameres. ILK binds the cytoplasmic domain of β1 integrin and mediates phosphorylation of protein kinase B (PKB)/Akt, which in turn plays a central role during skeletal muscle regeneration. We show that mice with a skeletal muscle–restricted deletion of ILK develop a mild progressive muscular dystrophy mainly restricted to the MTJs with detachment of basement membranes and accumulation of extracellular matrix. Endurance exercise training enhances the defects at MTJs, leads to disturbed subsarcolemmal myofiber architecture, and abrogates phosphorylation of Ser473 as well as phosphorylation of Thr308 of PKB/Akt. The reduction in PKB/Akt activation is accompanied by an impaired insulin-like growth factor 1 receptor (IGF-1R) activation. Coimmunoprecipitation experiments reveal that the β1 integrin subunit is associated with the IGF-1R in muscle cells. Our data identify the β1 integrin–ILK complex as an important component of IGF-1R/insulin receptor substrate signaling to PKB/Akt during mechanical stress in skeletal muscle. The Rockefeller University Press 2008-03-10 /pmc/articles/PMC2265410/ /pubmed/18332223 http://dx.doi.org/10.1083/jcb.200707175 Text en Copyright © 2008, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Wang, Hao-Ven Chang, Ling-Wei Brixius, Klara Wickström, Sara A. Montanez, Eloi Thievessen, Ingo Schwander, Martin Müller, Ulrich Bloch, Wilhelm Mayer, Ulrike Fässler, Reinhard Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage |
title | Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage |
title_full | Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage |
title_fullStr | Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage |
title_full_unstemmed | Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage |
title_short | Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage |
title_sort | integrin-linked kinase stabilizes myotendinous junctions and protects muscle from stress-induced damage |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265410/ https://www.ncbi.nlm.nih.gov/pubmed/18332223 http://dx.doi.org/10.1083/jcb.200707175 |
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