Nebulin, a major player in muscle health and disease

被引:53
作者
Labeit, Siegfried [1 ]
Ottenheijm, Coen A. C. [2 ]
Granzier, Henk [3 ]
机构
[1] Heidelberg Univ, Univ Med Mannheim, Dept Integrat Pathophysiol, D-68167 Mannheim, Germany
[2] Univ Amsterdam, VU Univ Med Ctr, Inst Cardiovasc Res, Physiol Lab, NL-1012 WX Amsterdam, Netherlands
[3] Univ Arizona, Dept Physiol, Tucson, AZ USA
基金
美国国家卫生研究院;
关键词
muscle contraction; regulation; calcium sensitivity; nemaline myopathy; sarcolipin; THIN FILAMENT LENGTH; RECESSIVE NEMALINE MYOPATHY; SKELETAL-MUSCLE; STRIATED-MUSCLE; AMPHIOXUS NEBULIN; CARDIAC-MUSCLE; GENE SEQUENCE; Z-DISC; MUTATIONS; PROTEIN;
D O I
10.1096/fj.10-157412
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nebulin is a giant 600- to 900-kDa filamentous protein that is an integral component of the skeletal muscle thin filament. Its functions have remained largely nebulous because of its large size and the difficulty in extracting nebulin in a native state from muscle. Recent improvements in the field, especially the development of knockout mouse models deficient in nebulin (NEB-KO mice), indicate now that nebulin performs a surprisingly wide range of functions. In addition to a major role in thin-filament length specification, nebulin also functions in the regulation of muscle contraction, as indicated by the findings that muscle fibers deficient in nebulin have a higher tension cost, and develop less force due to reduced myofilament calcium sensitivity and altered crossbridge cycling kinetics. In addition, the function of nebulin extends to a role in calcium homeostasis. These novel functions indicate that nebulin might have evolved in vertebrate skeletal muscles to develop high levels of muscle force efficiently. Finally, the NEB-KO mouse models also highlight the role of nebulin in the assembly and alignment of the Z disks. Notably, rapid progress in understanding the roles of nebulin in vivo provides clinically important insights into how nebulin deficiency in patients with nemaline myopathy contributes to debilitating muscle weakness.-Labeit, S., Ottenheijm, C. A. C., Granzier, H. Nebulin, a major player in muscle health and disease. FASEB J. 25, 822-829 (2011). www.fasebj.org
引用
收藏
页码:822 / 829
页数:8
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