Progressive myopathy and defects in the maintenance of myotendinous junctions in mice that lack talin 1 in skeletal muscle

Francesco J. Conti, Amanda Felder, Sue Monkley, Martin Schwander, Malcolm R. Wood, Richard Lieber, David Crithcley, Ulrich Müller

Research output: Contribution to journalArticlepeer-review

Abstract

The development and function of skeletal muscle depend on molecules that connect the muscle fiber cytoskeleton to the extracellular matrix (ECM). β1 integrins are ECM receptors in skeletal muscle, and mutations that affect the α7β1 integrin cause myopathy in humans. In mice, β1 integrins control myoblast fusion, the assembly of the muscle fiber cytoskeleton, and the maintenance of myotendinous junctions (MTJs). The effector molecules that mediate β1 integrin functions in muscle are not known. Previous studies have shown that talin 1 controls the force-dependent assembly of integrin adhesion complexes and regulates the affinity of integrins for ligands. Here we show that talin 1 is essential in skeletal muscle for the maintenance of integrin attachment sites at MTJs. Mice with a skeletal muscle-specific ablation of the talin 1 gene suffer from a progressive myopathy. Surprisingly, myoblast fusion and the assembly of integrin-containing adhesion complexes at costameres and MTJs advance normally in the mutants. However, with progressive ageing, the muscle fiber cytoskeleton detaches from MTJs. Mechanical measurements on isolated muscles show defects in the ability of talin 1-deficient muscle to generate force. Collectively, our findings show that talin 1 is essential for providing mechanical stability to integrin-dependent adhesion complexes at MTJs, which is crucial for optimal force generation by skeletal muscle.

Original languageEnglish (US)
Pages (from-to)2043-2053
Number of pages11
JournalDevelopment
Volume135
Issue number11
DOIs
StatePublished - Jun 2008
Externally publishedYes

Keywords

  • Integrin
  • Mouse
  • Muscular dystrophy
  • Myopathy
  • Talin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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