Shimada Eriko, Kinoshita Masato, Murata Kenji
Department of Animal Science, University of California, Davis, Davis, California 95616, USA.
Dev Growth Differ. 2009 Jan;51(1):1-16. doi: 10.1111/j.1440-169X.2008.01074.x.
Cardiac myosin light chain 2 (MLC-2) plays a key role in heart development, contraction, and embryo and adult heart maintenance. In some animals, defects in the function of cardiac MLC-2 cause hypertrophic cardiomyopathy. To illuminate the functions of cardiac MLC-2 in embryonic heart formation and contraction, and into the evolution of MLC-2, we characterized the expression and requirement for medaka cardiac MLC-2 gene in the developing heart. Medaka cardiac MLC-2 cDNA (mcmlc2) was isolated and its gene expression pattern was determined. The mcmlc2 was found to be expressed in the bilateral cardiac mesoderm, the formed heart tube, and in both the differentiated ventricle and atrium. Knockdown of mcmlc2 function caused severe cardiac disorders, including edema in the atrium and sinus venosus. Using phylogenetic analysis, we found that physiological variations in the MLC-2 molecules evolved due to amino acid changes in the Ca(2+) binding domain during molecular evolution. Our findings concerning the function and expression of mcmlc2 are nearly identical with those of other MLC-2 genes, and our phylogenetic analysis suggests that during evolution, the variations in physiological function within the MLC-2 gene family have arisen from a change in the amino acids in the Ca(2+) binding domain in the MLC-2 molecule.
心肌肌球蛋白轻链2(MLC-2)在心脏发育、收缩以及胚胎和成年心脏维持中起着关键作用。在一些动物中,心肌MLC-2功能缺陷会导致肥厚型心肌病。为了阐明心肌MLC-2在胚胎心脏形成和收缩中的功能以及MLC-2的进化,我们对青鳉心脏发育过程中心肌MLC-2基因的表达和需求进行了表征。分离出青鳉心肌MLC-2 cDNA(mcmlc2)并确定其基因表达模式。发现mcmlc2在双侧心脏中胚层、形成的心管以及分化的心室和心房中均有表达。敲低mcmlc2功能会导致严重的心脏疾病,包括心房和静脉窦水肿。通过系统发育分析,我们发现MLC-2分子的生理变异是由于分子进化过程中Ca(2+)结合域中的氨基酸变化而产生的。我们关于mcmlc2功能和表达的发现与其他MLC-2基因的发现几乎相同,并且我们的系统发育分析表明,在进化过程中,MLC-2基因家族内生理功能的变异源于MLC-2分子中Ca(2+)结合域中氨基酸的变化。