Nonmuscle Myosin II-C and its Isoform

非肌球蛋白ii在细胞分裂、细胞迁移和建立细胞极性过程中起重要作用。非肌肉肌球蛋白重链II （NMHC）的三种亚型已在脊椎动物中被鉴定，分别是NMHC II- a、II- b和II- c。对于NMHC II-C，另一个编码8个氨基酸的外显子被引入到loop1 （NMHC II-C1）中，另一个编码41个氨基酸的外显子被引入到loop2 （NMHC II-C2）中，位于NMHC中插入的NMHC II-B的同源位置。NMHC II-C2的组织分布与II-B1相似，II-B2局限于神经元组织，而NMHC II-C1在多种组织中表达，如肝、肾、睾丸、脑和肺。我们最近报道了一些肿瘤细胞系中NMHC II-C1异构体的表达明显增加，抑制表达导致细胞质分裂延迟，从而导致A549人肺肿瘤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，我们使用同源重组产生了半胚敲除小鼠。这些小鼠表达的肌球蛋白II-C量减少，都缺乏c1插入物。其中一些小鼠通过超声心动图和组织病理学分析显示有心肌病的迹象。值得注意的是，NMHC II-C1在心脏中的表达仅限于胚胎期。

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.