Effect of Cardiomyopathic Mutations in Tropomyosin on Calcium Regulation of the Actin-Myosin Interaction in Skeletal Muscle

被引:7
作者
Kopylova, G. V. [1 ]
Shchepkin, D. V. [1 ]
Borovkov, D. I. [1 ,2 ]
Matyushenko, A. M. [3 ]
机构
[1] Russian Acad Sci, Inst Immunol & Physiol, Ural Div, Moscow, Russia
[2] BN Yeltsin Ural Fed Univ, Ekaterinburg, Russia
[3] Russian Acad Sci, Fed Res Ctr Biotechnol, AN Bach Inst Biochem, Moscow, Russia
基金
俄罗斯基础研究基金会;
关键词
tropomyosin; actin-myosin interaction; calcium regulation; in vitro motility assay; ALPHA-TROPOMYOSIN; HYPERTROPHIC CARDIOMYOPATHY; THIN-FILAMENTS; SENSITIVITY;
D O I
10.1007/s10517-016-3540-x
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Tropomyosin plays an important role in the regulation of actin-myosin interaction in striated muscles. Mutations in the tropomyosin gene disrupt actin-myosin interaction and lead to myopathies and cardiomyopathies. Tropomyosin with mutations in the a-chain is expressed in both the myocardium and skeletal muscles. We studied the effect of mutations in the a-chain of tropomyosin related to hypertrophic (D175N and E180G) and dilated cardiomyopathies (E40K and E54K) on calcium regulation of the actin-myosin interaction in skeletal muscles. We analyzed the calcium-dependent sliding velocity of reconstructed thin filaments containing F-actin, troponin, and tropomyosin over myosin surface in an in vitro motility assay. Mutations D175N and E180G in tropomyosin increased the sliding velocity and its calcium sensitivity, while mutation E40K reduced both these parameters. E54K mutation increased the sliding velocity of thin filaments, but did not affect its calcium sensitivity.
引用
收藏
页码:42 / 44
页数:3
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