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Indications for a novel muscular dystrophy pathway. gamma-filamin, the muscle-specific filamin isoform, interacts with myotilin.

gamma-Filamin, also called ABP-L, is a filamin isoform that is specifically expressed in striated muscles, where it is predominantly localized in myofibrillar Z-discs. A minor fraction of the protein shows subsarcolemmal localization. Although gamma-filamin has the same overall structure as the two other known isoforms, it is the only isoform that carries a unique insertion in its immunoglobulin (Ig)-like domain 20. Sequencing of the genomic region encoding this part of the molecule shows that this insert is encoded by an extra exon. Transient transfections of the insert-bearing domain in skeletal muscle cells and cardiomyocytes show that this single domain is sufficient for targeting to developing and mature Z-discs. The yeast two-hybrid method was used to identify possible binding partners for the insert-bearing Ig-like domain 20 of gamma-filamin. The two Ig-like domains of the recently described alpha-actinin-binding Z-disc protein myotilin were found to interact directly with this filamin domain, indicating that the amino-terminal end of gamma-filamin may be indirectly anchored to alpha-actinin in the Z-disc via myotilin. Since defects in the myotilin gene were recently reported to cause a form of autosomal dominant limb-girdle muscular dystrophy, our findings provide a further contribution to the molecular understanding of this disease.

Pubmed ID: 11038172


  • van der Ven PF
  • Wiesner S
  • Salmikangas P
  • Auerbach D
  • Himmel M
  • Kempa S
  • Hayess K
  • Pacholsky D
  • Taivainen A
  • Schröder R
  • Carpén O
  • Fürst DO


The Journal of cell biology

Publication Data

October 16, 2000

Associated Grants


Mesh Terms

  • Adult
  • Animals
  • Cell Differentiation
  • Connectin
  • Contractile Proteins
  • Cytoskeletal Proteins
  • DNA Transposable Elements
  • Exons
  • Filamins
  • Humans
  • Immunoglobulins
  • Ligands
  • Mice
  • Microfilament Proteins
  • Muscle Proteins
  • Muscle, Skeletal
  • Muscular Dystrophies
  • Myocardium
  • Myofibrils
  • Protein Binding
  • Protein Isoforms
  • Protein Sorting Signals
  • Protein Structure, Tertiary
  • Stem Cells
  • Two-Hybrid System Techniques