Filamin C plays an essential role in the maintenance of the structural integrity of cardiac and skeletal muscles, revealed by the medaka mutant zacro

被引：82

作者：

Fujita, Misato ^{[1
]}

Mitsuhashi, Hiroaki ^{[2
]}

Isogai, Sumio ^{[3
]}

Nakata, Takahiro ^{[4
]}

Kawakami, Atsushi ^{[1
]}

Nonaka, Ikuya ^{[2
]}

Noguchi, Satoru ^{[2
]}

Hayashi, Yukiko K. ^{[2
]}

Nishino, Ichizo ^{[2
]}

Kudo, Akira ^{[1
]}

机构：

[1] Tokyo Inst Technol, Dept Biol Informat, Midori Ku, Yokohama, Kanagawa 2268501, Japan

[2] Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Neuromuscular Res, Kodaira, Tokyo 1878502, Japan

[3] Iwate Med Univ, Sch Med, Dept Anat, Yahaba, Shiwa 0283694, Japan

[4] Ishikawa Prefectural Nursing Univ, Dept Hlth Sci, Kahoku, Ishikawa 9291210, Japan

来源：

DEVELOPMENTAL BIOLOGY | 2012年 / 361卷 / 01期

基金：

日本学术振兴会;

关键词：

Medaka mutant; Filamin C; Cardiac muscle; Skeletal muscle; zacro; RECESSIVE MUSCULAR-DYSTROPHY; RABBIT ALVEOLAR MACROPHAGES; ACTIN-BINDING PROTEIN; ORYZIAS-LATIPES; Z-DISC; ALPHA-7-BETA-1; INTEGRIN; MYOFIBRILLAR MYOPATHY; MYOTENDINOUS JUNCTION; DELTA-SARCOGLYCAN; DEVELOPMENTAL GENETICS;

D O I：

10.1016/j.ydbio.2011.10.008

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 (flu) 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 gamma-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. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：79 / 89

页数：11

共 81 条

[1] Dystrophin-glycoprotein complex and vinculin-talin-integrin system in human adult cardiac muscle [J].