Integrin-linked Kinase Stabilizes Myotendinous Junctions and Protects Muscle from Stress-induced Damage

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2008 Mar 12

PMID 18332223

Citations 51

Authors

Hao-Ven Wang

Ling-Wei Chang

Klara Brixius

Sara A Wickstrom

Eloi Montanez

Ingo Thievessen

Martin Schwander

Ulrich Muller

Wilhelm Bloch

Ulrike Mayer

Reinhard Fassler

Affiliations

Soon will be listed here.

Abstract

Skeletal muscle expresses high levels of integrin-linked kinase (ILK), predominantly at myotendinous junctions (MTJs) and costameres. ILK binds the cytoplasmic domain of beta1 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 beta1 integrin subunit is associated with the IGF-1R in muscle cells. Our data identify the beta1 integrin-ILK complex as an important component of IGF-1R/insulin receptor substrate signaling to PKB/Akt during mechanical stress in skeletal muscle.

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