Impact of sarcoglycan complex on mechanical signal transduction in murine skeletal muscle

被引:67
作者
Barton, ER
机构
[1] Univ Penn, Dept Anat & Cell Biol, Sch Dent Med, Philadelphia, PA 19104 USA
[2] Univ Penn, Penn Muscle Inst, Philadelphia, PA 19104 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2006年 / 290卷 / 02期
关键词
muscular dystrophy; eccentric contractions; extracellular signal-regulated kinase 1/2;
D O I
10.1152/ajpcell.00192.2005
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Loss of the dystrophin glycoprotein complex (DGC) or a subset of its components can lead to muscular dystrophy. However, the patterns of symptoms differ depending on which proteins are affected. Absence of dystrophin leads to loss of the entire DGC and is associated with susceptibility to contractile injury. In contrast, muscles lacking gamma-sarcoglycan (gamma-SG) display little mechanical fragility and still develop severe pathology. Animals lacking dystrophin or gamma-SG were used to identify DGC components critical for sensing dynamic mechanical load. Extensor digitorum longus muscles from 7-wk-old normal (C57), dystrophin-null (mdx), and gamma-SG-null (gsg(-/-)) mice were subjected to a series of eccentric contractions, after which ERK1/2 phosphorylation levels were determined. At rest, both dystrophic strains had significantly higher ERK1 phosphorylation, and gsg(-/-) muscle also had heightened ERK2 phosphorylation compared with wild-type controls. Eccentric contractions produced a significant and transient increase in ERK1/2 phosphorylation in normal muscle, whereas the mdx strain displayed no significant proportional change of ERK1/2 phosphorylation after eccentric contraction. Muscles from gsg(-/-) mice had no significant increase in ERK1 phosphorylation; however, ERK2 phosphorylation was more robust than in C57 controls. The reduction in mechanically induced ERK1 phosphorylation in gsg(-/-) muscle was not dependent on age or severity of phenotype, because muscle from both young and old (age 20 wk) animals exhibited a reduced response. Immunoprecipitation experiments revealed that gamma-SG was phosphorylated in normal muscle after eccentric contractions, indicating that members of the DGC are modified in response to mechanical perturbation. This study provides evidence that the SGs are involved in the transduction of mechanical information in skeletal muscle, potentially unique from the entire DGC.
引用
收藏
页码:C411 / C419
页数:9
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