RRC ID 30897
Author Fujita M, Mitsuhashi H, Isogai S, Nakata T, Kawakami A, Nonaka I, Noguchi S, Hayashi YK, Nishino I, Kudo A.
Title Filamin C plays an essential role in the maintenance of the structural integrity of cardiac and skeletal muscles, revealed by the medaka mutant zacro.
Journal Dev Biol
Abstract Filamin C is an actin-crosslinking protein that is specifically expressed in cardiac and skeletal muscles. Although mutations in the filamin C gene cause human myopathy with cardiac involvement, the function of filamin C in vivo is not yet fully understood. Here we report a medaka mutant, zacro (zac), that displayed an enlarged heart, caused by rupture of the myocardiac wall, and progressive skeletal muscle degeneration in late embryonic stages. We identified zac to be a homozygous nonsense mutation in the filamin C (flnc) gene. The medaka filamin C protein was found to be localized at myotendinous junctions, sarcolemma, and Z-disks in skeletal muscle, and at intercalated disks in the heart. zac embryos showed prominent myofibrillar degeneration at myotendinous junctions, detachment of myofibrils from sarcolemma and intercalated disks, and focal Z-disk destruction. Importantly, the expression of γ-actin, which we observed to have a strong subcellular localization at myotendinous junctions, was specifically reduced in zac mutant myotomes. Inhibition of muscle contraction by anesthesia alleviated muscle degeneration in the zac mutant. These results suggest that filamin C plays an indispensable role in the maintenance of the structural integrity of cardiac and skeletal muscles for support against mechanical stress.
Volume 361(1)
Pages 79-89
Published 2012-1-1
DOI 10.1016/j.ydbio.2011.10.008
PII S0012-1606(11)01314-5
PMID 22020047
MeSH Actins / metabolism Animals Birefringence Cardiomegaly / genetics* Cloning, Molecular Codon, Nonsense / genetics Contractile Proteins / genetics* Contractile Proteins / metabolism* DNA Primers / genetics Filamins Fluorescent Antibody Technique In Situ Hybridization Microfilament Proteins / genetics* Microfilament Proteins / metabolism* Microscopy, Electron, Transmission Muscle, Skeletal / metabolism* Muscular Disorders, Atrophic / genetics* Myocardium / metabolism* Oligonucleotides, Antisense / genetics Oryzias / embryology* Oryzias / genetics Polymorphism, Restriction Fragment Length / genetics Sarcolemma / pathology
IF 2.896
Times Cited 60
Medaka MT326