Roles of Nebulin Family Members in the Heart

被引:36
作者
Bang, Marie-Louise [1 ,2 ]
Chen, Ju [3 ]
机构
[1] UOS Milan, Inst Genet & Biomed Res, CNR, I-20089 Milan, Italy
[2] Humanitas Clin & Res Ctr, Milan, Italy
[3] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
基金
美国国家卫生研究院;
关键词
Dilated cardiomyopathy; N-RAP; Nebulette; Nebulin family; THIN FILAMENT LENGTH; CULTURED CHICK CARDIOMYOCYTES; SKELETAL-MUSCLE SARCOMERE; ACTIN-BINDING PROTEIN; N-RAP; STRIATED-MUSCLE; DILATED CARDIOMYOPATHY; LIM PROTEIN; Z-DISC; NEMALINE MYOPATHY;
D O I
10.1253/circj.CJ-15-0854
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The members of the nebulin protein family, including nebulin, nebulette, LASP-1, LASP-2, and N-RAP, contain various numbers of nebulin repeats and bind to actin, but are otherwise heterogeneous with regard to size, expression pattern, and function. This review focuses on the roles of nebulin family members in the heart. Nebulin is the largest member predominantly expressed in skeletal muscle, where it stretches along the thin filament. In heart, nebulin is detectable only at low levels and its absence has no apparent effects. Nebulette is similar in structure to the nebulin C-terminal Z-line region and specifically expressed in heart. Nebulette gene mutations have been identified in dilated cardiomyopathy patients and transgenic mice overexpressing nebulette mutants partially recapitulate the human pathology. In contrast, nebulette knockout mice show no functional phenotype, but exhibit Z-line widening. LASP-2 is an isoform of nebulette expressed in multiple tissues, including the heart. It is present in the Z-line and intercalated disc and able to bind and cross-link filamentous actin. LASP-1 is similar in structure to LASP-2, but expressed only in non-muscle tissue. N-RAP is present in myofibril precursors during myofibrillogenesis and thought to be involved in myofibril assembly, while it is localized at the intercalated disc in adult heart. Additional in vivo models are required to provide further insights into the functions of nebulin family members in the heart.
引用
收藏
页码:2081 / 2087
页数:7
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