Nonmuscle Myosin II-C and its Isoform

非肌肉肌球蛋白II在胞质分裂、细胞迁移和确定细胞极性方面发挥着重要作用。脊椎动物的非肌球蛋白重链II(NMHC)有三种亚型，即NMHC II-A、II-B和II-C。对于NMHC II-C，编码8个氨基酸的替代外显子被引入到loop1(NMHC II-C1)中，而另一个编码41个氨基酸的替代外显子被引入到Loop2(NMHC II-C2)中，其位置与NMHC II-B的插入序列同源。NMHC II-C2的组织分布与II-B1相似，II-B2仅限于神经元组织，而NMHC II-C1表达于肝、肾、睾丸、脑和肺等多种组织。我们最近报道，在一些肿瘤细胞系中，NMHC II-C1亚型的表达显著增加，并且抑制表达导致胞质分裂延迟，从而导致A549人肺癌细胞系细胞增殖下降。为了在体内研究非肌肉肌球蛋白II-C1的功能，我们利用同源重组产生了亚型基因敲除小鼠。这些小鼠表达的肌球蛋白II-C数量减少，所有这些都缺乏C1-插入。通过超声心动图和组织病理学分析，这些小鼠中的一些显示出心肌病的证据。值得注意的是，NMHC II-C1在心脏中的表达仅限于胚胎阶段。

Nonmuscle myosin IIs play an important role during cytokinesis, cell migration and in establishing cell polarity. Three isoforms of nonmuscle myosin heavy chain II (NMHC) have been identified in vertebrates, NMHC II-A, II-B and II-C. For NMHC II-C, an alternative exon encoding 8 amino acids is incorporated into loop1 (NMHC II-C1) and another alternative exon encoding 41 amino acids is introduced into loop2 (NMHC II-C2) at homologous locations to the NMHC II-B inserts in the NMHC. Whereas the tissue distribution of NMHC II-C2 is similar to that of II-B1 and II-B2 is being confined to neuronal tissue, NMHC II-C1 is expressed in a variety of tissues, such as liver, kidney, testes, brain and lung. We recently reported that the expression of NMHC II-C1 isoform is markedly increased in some tumor cell lines and that inhibiting expression leads to a delay in cytokinesis, resulting in a decrease in cell proliferation in the A549 human lung tumor cell line. For in vivo study of nonmuscle myosin II-C1 function, we generated hypomorphic knockout mice using homologous recombination. These mice expressed decreased amounts of myosin II-C, all of which lacked the C1-insert. Some of these mice show evidence for a cardiomyopathy as determined by echocardiography and histopathologic analysis. Of note is that expression of NMHC II-C1 in the heart is restricted to the embryonic stage.