Filamin actin-binding and titin-binding fulfill distinct functions in Z-disc cohesion

PLoS Genet. 2017 Jul 21;13(7):e1006880. doi: 10.1371/journal.pgen.1006880. eCollection 2017 Jul.


Many proteins contribute to the contractile properties of muscles, most notably myosin thick filaments, which are anchored at the M-line, and actin thin filaments, which are anchored at the Z-discs that border each sarcomere. In humans, mutations in the actin-binding protein Filamin-C result in myopathies, but the underlying molecular function is not well understood. Here we show using Drosophila indirect flight muscle that the filamin ortholog Cheerio in conjunction with the giant elastic protein titin plays a crucial role in keeping thin filaments stably anchored at the Z-disc. We identify the filamin domains required for interaction with the titin ortholog Sallimus, and we demonstrate a genetic interaction of filamin with titin and actin. Filamin mutants disrupting the actin- or the titin-binding domain display distinct phenotypes, with Z-discs breaking up in parallel or perpendicularly to the myofibril, respectively. Thus, Z-discs require filamin to withstand the strong contractile forces acting on them.

MeSH terms

  • Actin Cytoskeleton / genetics
  • Actin Cytoskeleton / metabolism
  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Connectin / genetics*
  • Connectin / metabolism
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Filamins / genetics*
  • Filamins / metabolism
  • Flight, Animal
  • Humans
  • Muscle Contraction / genetics
  • Muscle, Skeletal / metabolism
  • Myofibrils / genetics*
  • Myofibrils / metabolism
  • Phenotype
  • Protein Binding
  • RNA Interference
  • Sarcomeres / genetics
  • Sarcomeres / metabolism


  • Actins
  • Connectin
  • Drosophila Proteins
  • Filamins
  • cher protein, Drosophila
  • sls protein, Drosophila

Grant support

This work was supported by operating grant MOP-142475 from the Canadian Institutes of Health Research ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.