PUBLICATION

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

Authors
Postel, R., Vakeel, P., Topczewski, J., Knöll, R., and Bakkers, J.
ID
ZDB-PUB-080429-10
Date
2008
Source
Developmental Biology   318(1): 92-101 (Journal)
Registered Authors
Bakkers, Jeroen, Postel, Ruben, Topczewski, Jacek
Keywords
Myotendinous junctions, ILK, Integrin, Laminin, loc, Zebrafish, Muscular dystrophy, MLP, β-parvin
MeSH Terms
  • Humans
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Zebrafish*/anatomy & histology
  • Zebrafish*/embryology
  • Zebrafish*/metabolism
  • Phylogeny
  • Cytoskeleton/metabolism
  • Recombinant Fusion Proteins/genetics
  • Recombinant Fusion Proteins/metabolism
  • Antigens, CD/classification
  • Antigens, CD/genetics
  • Antigens, CD/metabolism*
  • Oligonucleotides, Antisense/genetics
  • Oligonucleotides, Antisense/metabolism
  • Two-Hybrid System Techniques
  • Animals
  • Phenotype
  • Actinin/genetics
  • Actinin/metabolism
  • Cell Adhesion/physiology*
  • Lim Kinases/genetics
  • Lim Kinases/metabolism
  • Extracellular Matrix/genetics
  • Extracellular Matrix/metabolism*
  • Muscle, Skeletal*/cytology
  • Muscle, Skeletal*/embryology
  • Muscle, Skeletal*/metabolism
  • Protein Serine-Threonine Kinases/genetics
  • Protein Serine-Threonine Kinases/metabolism*
  • Laminin/genetics
  • Laminin/metabolism
  • Integrin alpha Chains/classification
  • Integrin alpha Chains/genetics
  • Integrin alpha Chains/metabolism*
  • Paxillin/genetics
  • Paxillin/metabolism
(all 37)
PubMed
18436206 Full text @ Dev. Biol.
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, itgalpha7, Ilk and beta-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 itgalpha7 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 itgalpha7, providing strengthening of skeletal muscle fibre adhesion with the ECM and therefore qualified as a novel candidate gene for congenital muscular dystrophy.
Genes / Markers
Figures
Figure Gallery (12 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hu801
    Point Mutation
    vu119TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      csrp3MO1-csrp3MRPHLNO
      dag1MO1-dag1MRPHLNO
      ilkMO2-ilkMRPHLNO
      itga7MO1-itga7MRPHLNO
      itga7MO2-itga7MRPHLNO
      lama2MO1-lama2MRPHLNO
      lama4MO1-lama4MRPHLNO
      parvbMO1-parvbMRPHLNO
      1 - 8 of 8
      Show
      Fish
      Antibodies
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
      GFPEFGGFP
      1 - 2 of 2
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      Mapping
      No data available