The role of the N-terminus of the myosin essential light chain in cardiac muscle contraction.
The role of the N-terminus of the myosin essential light chain in cardiac muscle contraction.
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DOI：
10.1016/j.jmb.2009.02.006
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发表时间：
2009-04-03
影响因子：
5.6
通讯作者：
Szczesna-Cordary D
中科院分区：
文献类型：
--
作者：
Kazmierczak K;Xu Y;Jones M;Guzman G;Hernandez OM;Kerrick WG;Szczesna-Cordary D
为了研究肌球蛋白必需轻链（myosin essential light chain， ELC）对心肌收缩的调控及其n端延伸的生理意义，我们在小鼠心脏中用人心室ELC野生型（Tg- wt）或其43个氨基酸n端截断突变体（Tg-Δ43）部分替代内源性小鼠心室ELC，制备了转基因（Tg）小鼠。突变蛋白的序列与骨骼肌中存在的短ELC变异相似，而Tg-Δ43心室中的ELC蛋白分布与快速骨骼肌相似。Tg-Δ43小鼠的心肌制剂显示肌肉每横截面积的力降低，这可能是由于产生肌球蛋白交叉桥的力数量减少和/或每个交叉桥的力降低所致。随着小鼠年龄的增长，Tg-Δ43小鼠每横截面积的收缩力进一步降低，突变心脏在保持正常心脏功能的同时出现非病理性肥大的表型。老年Tg-Δ43小鼠心肌肌球蛋白含量也降低。我们的研究结果表明，n端ELC延伸的作用是维持肌凝蛋白的完整性，并通过降低肌凝蛋白颈部顺应性和促进强交叉桥形成和/或通过增强肌凝蛋白与肌动蛋白的附着来调节力的产生。
To study the regulation of cardiac muscle contraction by the myosin essential light chain (ELC) and the physiological significance of its N-terminal extension, we generated transgenic (Tg) mice partially replacing the endogenous mouse ventricular ELC with either the human ventricular ELC wild type (Tg-WT) or its 43 amino acid N-terminal truncation mutant (Tg-Δ43) in the murine hearts. The mutant protein is similar in sequence to the short ELC variant present in skeletal muscle and the ELC protein distribution in Tg-Δ43 ventricles resembles that of fast skeletal muscle. Cardiac muscle preparations from Tg-Δ43 mice demonstrate reduced force per cross-sectional area of muscle, which is likely caused by a reduced number of force generating myosin cross-bridges and/or by decreased force per cross-bridge. As the mice grow older, the contractile force per cross-sectional area further decreases in Tg-Δ43 mice and the mutant hearts develop a phenotype of non-pathologic hypertrophy while still maintaining normal cardiac performance. The myocardium of older Tg-Δ43 mice also exhibits reduced myosin content. Our results suggest that the role of the N-terminal ELC extension is to maintain the integrity of myosin and to modulate force generation by decreasing myosin neck region compliance and promoting strong cross-bridge formation and/or by enhancing myosin attachment to actin.