Selective requirement of myosin light chain 2v in embryonic heart function
Selective requirement of myosin light chain 2v in embryonic heart function
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DOI：
10.1074/jbc.273.2.1252
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发表时间：
1998-01-09
影响因子：
4.8
通讯作者：
Chien, KR
中科院分区：
文献类型：
--
作者：
Chen, J;Kubalak, SW;Chien, KR
两个主要的肌球蛋白轻链2亚型在小鼠心脏发生的早期阶段共表达，一个是心室亚型，另一个是心房亚型，在胚胎发生期间，每一个亚型都以特定肌细胞类型的方式受到严格的调控(Chien，K.R.，朱，H.，Knowlton，K.U，Miller-Hance，W.，van Bilsen，M.，O‘Brien，T.X.和Evans，S.M.(1993)Annu)。菲西奥尔牧师。55、77-95)。我们已经打乱了小鼠的肌球蛋白轻链2v基因，并在活体内监测了肌球蛋白轻链2v-/-胚胎的心脏功能，突变的胚胎大约在胚胎12.5天死亡。在突变的脑室中，肌球蛋白轻链2a的蛋白水平增加，并达到与野生型仔猪脑室中肌球蛋白轻链2v相当的水平，并适当地结合到突变胚胎心脏的粗丝中，然而，尽管肌球蛋白轻链2a被取代，超微结构分析揭示了肌球蛋白轻链2a的组装缺陷和扩张型心肌病的胚胎形式，其特征是突变胚胎的左心室射血分数显著低于野生型。我们认为，在哺乳动物心脏发生过程中，肌球蛋白轻链2v在维持心肌收缩能力和室腔形态形成方面可能具有独特的功能，并且可能存在一种肌球蛋白轻链2v的特定腔室组合密码，最终需要在心室肌细胞中使用肌球蛋白轻链2v。
Two major myosin light chain 2 isoforms are coexpressed in the early stages of murine cardiogenesis, a cardiac ventricular isoform and a cardiac atrial isoform, each of which is tightly regulated in a muscle cell-type-specific manner during embryogenesis (Chien, K. R., Zhu, H., Knowlton, K. U., Miller-Hance, W., van Bilsen, M., O'Brien, T. X., and Evans, S. M. (1993) Annu. Rev. Physiol. 55, 77-95). We have disrupted myosin light chain 2v gene in mice and monitored in vivo cardiac function in living myosin light chain 2v -/- embryos, The mutant embryos die at approximately embryonic day 12.5. In mutant ventricles, the myosin light chain 2a protein level is increased and reaches levels comparable to the myosin light chain 2v in the ventricles of wild type littermates and is appropriately incorporated into the thick filaments of mutant embryonic hearts, However despite the substitution of myosin light chain 2a, ultrastructural analysis revealed defects in sarcomeric assembly and an embryonic form of dilated cardiomyopathy characterized by a significantly reduced left ventricular ejection fraction in mutant embryos compared with wild type littermates, We conclude that myosin light chain 2v may have a unique function in the maintenance of cardiac contractility and ventricular chamber morphogenesis during mammalian cardiogenesis and that a chamber-specific combinatorial code for sarcomeric assembly may exist that ultimately requires myosin light chain 2v in ventricular muscle cells.