Nonmuscle Myosin II-C and its Isoform

Heart, Lung, And Blood Institute

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Abstract

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.