Zebrafish integrin-linked kinase is required in skeletal muscles for strengthening the integrin-ECM adhesion complex

Ruben Postel, Padmanabhan Vakeel, Jacek Topczewski, Ralph Knöll, Jeroen Bakkers*

*Corresponding author for this work

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Mechanical instability of skeletal muscle cells is the major cause of congenital muscular dystrophy. Here we show that the zebrafish lost-contact mutant, that lacks a functional integrin-linked kinase (ilk) gene, suffers from mechanical instability of skeletal muscle fibres. With genetic and morpholino knock-down experiments we demonstrate that: 1) laminin, itgα7, Ilk and β-parvin are all critical for mechanical stability in skeletal muscles. 2) Ilk acts redundantly with the dystrophin/dystroglycan adhesion complex in maintaining mechanical stability of skeletal muscles. 3) Ilk protein is recruited to the myotendinous junctions, which requires the ECM component laminin and the presence of itgα7 in the sarcolemma. 4) Ilk, unexpectedly, is dispensable for formation of the adhesion complex. Ilk, however, is required for strengthening the adhesion of the muscle fibre with the ECM and this activity requires the presence of a functional kinase domain in Ilk. 5) We identified a novel interaction between Ilk and the mechanical stretch sensor protein MLP. Thus, Ilk is an essential intracellular component downstream of laminin and itgα7, providing strengthening of skeletal muscle fibre adhesion with the ECM and therefore qualified as a novel candidate gene for congenital muscular dystrophy.

Original languageEnglish (US)
Pages (from-to)92-101
Number of pages10
JournalDevelopmental Biology
Volume318
Issue number1
DOIs
StatePublished - Jun 1 2008

Keywords

  • ILK
  • Integrin
  • Laminin
  • MLP
  • Muscular dystrophy
  • Myotendinous junctions
  • Zebrafish
  • loc
  • β-parvin

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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