Functions of myosin light chain-2 (MYL2) in cardiac muscle and disease.
Functions of myosin light chain-2 (MYL2) in cardiac muscle and disease.
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DOI：
10.1016/j.gene.2015.06.027
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发表时间：
2015-09-10
期刊：
影响因子：
3.5
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Sheikh F;Lyon RC;Chen J
肌球蛋白轻链-2（Myosin light chain-2，MYL 2，也称为MLC-2）是属于EF-手型钙结合蛋白超家族的约19 kDa的肌节蛋白，并且在哺乳动物横纹肌中以由三个不同基因编码的三种主要同种型存在。三种不同的MLC-2基因（MLC-2f;快缩骨骼同种型，MLC-2 v;心室和慢缩骨骼同种型，MLC-2a;心房同种型）中的每一种在哺乳动物中具有不同的发育表达模式。在小鼠中进行的遗传功能丧失研究表明，MLC-2、MLC-2 v和MLC-2a的心脏同种型在早期胚胎发生期间的心脏收缩功能中具有重要作用。在成人心脏中，MLC-2 v功能受磷酸化调节，磷酸化在整个心脏中显示出特定的表达模式（心外膜高，内膜低）。这些数据沿着来自计算模型、遗传小鼠模型和人类研究的新数据，揭示了MLC-2 v磷酸化在跨桥循环动力学、钙依赖性心肌收缩、心脏扭转、心脏功能和各种心脏疾病中的直接作用。本文综述了MLC-2在胚胎和成人心脏中的调节功能，重点介绍了MLC-2 v在成人心肌中的磷酸化驱动作用，为研究肌球蛋白循环动力学调控机制和人类心脏疾病提供了新的视角。
Myosin light chain-2 (MYL2, also called MLC-2) is an ∼19 kDa sarcomeric protein that belongs to the EF-hand calcium binding protein superfamily and exists as three major isoforms encoded by three distinct genes in mammalian striated muscle. Each of the three different MLC-2 genes (MLC-2f; fast twitch skeletal isoform, MLC-2v; cardiac ventricular and slow twitch skeletal isoform, MLC-2a; cardiac atrial isoform) has a distinct developmental expression pattern in mammals. Genetic loss-of-function studies in mice demonstrated an essential role for cardiac isoforms of MLC-2, MLC-2v and MLC-2a, in cardiac contractile function during early embryogenesis. In the adult heart, MLC-2v function is regulated by phosphorylation, which displays a specific expression pattern (high in epicardium and low in endocardium) across the heart. These data along with new data from computational models, genetic mouse models, and human studies have revealed a direct role for MLC-2v phosphorylation in cross-bridge cycling kinetics, calcium-dependent cardiac muscle contraction, cardiac torsion, cardiac function and various cardiac diseases. This review focuses on the regulatory functions of MLC-2 in the embryonic and adult heart, with an emphasis on phosphorylation-driven actions of MLC-2v in adult cardiac muscle, which provide new insights into mechanisms regulating myosin cycling kinetics and human cardiac diseases.
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影响因子：
4.6
作者：
Huang, CQ;Sheikh, F;Chen, J
通讯作者：
Chen, J
人类心脏肌球蛋白的分子表型与肥厚的阻塞性心肌病有关。
影响因子：
10.8
作者：
Jacques AM;Briceno N;Messer AE;Gallon CE;Jalilzadeh S;Garcia E;Kikonda-Kanda G;Goddard J;Harding SE;Watkins H;Esteban MT;Tsang VT;McKenna WJ;Marston SB
通讯作者：
Marston SB
影响因子：
1.2
作者：
Bizy, Alexandra;Guerrero-Serna, Guadalupe;Hu, Bin;Ponce-Balbuena, Daniela;Willis, B. Cicero;Zarzoso, Manuel;Ramirez, Rafael J.;Sener, Michelle F.;Mundada, Lakshmi V.;Klos, Matthew;Devaney, Eric J.;Vikstrom, Karen L.;Herron, Todd J.;Jalife, Jose
通讯作者：
Jalife, Jose
影响因子：
5
作者：
Huang, Wenrui;Liang, Jingsheng;Kazmierczak, Katarzyna;Muthu, Priya;Duggal, Divya;Farman, Gerrie P.;Sorensen, Lars;Pozios, Iraklis;Abraham, Theodore P.;Moore, Jeffrey R.;Borejdo, Julian;Szczesna-Cordary, Danuta
通讯作者：
Szczesna-Cordary, Danuta
影响因子：
4.8
作者：
Chen, J;Kubalak, SW;Chien, KR
通讯作者：
Chien, KR