Laboratory of Molecular Cardiology, NHLBI, National Institutes of Health, Bethesda, MD 20892, USA.
Front Biosci (Landmark Ed). 2012 Jan 1;17(2):545-55. doi: 10.2741/3942.
Nonmuscle myosin II-B (NM II-B) plays an important role in cardiac development and function. Genetic ablation of NM II-B in mice results in both cellular and structural defects involving cardiac myocytes. These abnormalities include a ventricular septal defect, double outlet of the right ventricle, myocyte hypertrophy and premature onset of myocyte binucleation due to abnormalities in cytokinesis. The mice die by embryonic day (E) 14.5 due to defects in heart development. Conditional ablation of NM II-B in cardiac myocytes after E11.5 allows study of NM II-B function in adult myocytes. BaMHC/BaMHC mice are born with enlarged cardiac myocytes, some of which are multinucleated. Between 6-10 months of age they develop a cardiomyopathy. Many of these mice develop a marked widening of the intercalated discs. The loss of NM II-B from the intercalated discs primarily affects the adhesion junctions rather than the gap junctions and desmosomes. Interestingly, the loss of NM II-B results in a decrease in the actin binding protein mXin which also has been shown to cause disruption of the intercalated disc in addition to cardiac arrhythmias (Gustafson-Wagner et al. Am J Physiol Heart Circ Physiol. 2007, 293:H2680-92). Finally we review the evidence showing that ablation of NM II-C (which also localizes to the intercalated disc) in mouse hearts deficient in NM II-B expression results in destabilization of N-cadherin and beta-catenin in the intercalated disc.
非肌肉肌球蛋白 II-B（NM II-B）在心脏发育和功能中发挥着重要作用。在小鼠中，NM II-B 的基因缺失会导致涉及心肌细胞的细胞和结构缺陷。这些异常包括室间隔缺损、右心室双出口、心肌细胞肥大和由于胞质分裂异常导致的心肌细胞双核化的提前发生。由于心脏发育缺陷，这些小鼠在胚胎第 14.5 天死亡。在 E11.5 后，在心肌细胞中条件性缺失 NM II-B 可研究 NM II-B 在成年心肌细胞中的功能。BaMHC/BaMHC 小鼠出生时心肌细胞增大，其中一些为多核。在 6-10 个月大时，它们会患上心肌病。其中许多小鼠出现明显的闰盘增宽。闰盘中 NM II-B 的丢失主要影响黏附连接，而不是间隙连接和桥粒。有趣的是，NM II-B 的丢失会导致肌动蛋白结合蛋白 mXin 的减少，mXin 也已被证明除了引起心律失常外，还会破坏闰盘（Gustafson-Wagner 等人，《美国生理学杂志-心脏循环生理学》，2007 年，293:H2680-92）。最后，我们综述了证据表明，在 NM II-B 表达缺失的小鼠心脏中，NM II-C（也定位于闰盘）的缺失会导致闰盘中 N-钙黏蛋白和β-连环蛋白的不稳定性。
