期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：33
页码：14645-14650
DOI：10.1073/pnas.1004023107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Nonmuscle myosins (NMs) II-A and II-B are essential for embryonic mouse development, but their specific roles are not completely defined. Here we examine the isoforms and their domain specifically in vivo and in vitro by studying mice and cells in which nonmuscle myosin heavy chain (NMHC) II-A is genetically replaced by NMHC II-B or chimeric NMHC IIs that exchange the rod and head domains of NM II-A and II-B. In contrast with the failure of visceral endoderm formation resulting in embryonic day (E)6.5 lethality of A-/A- mice, replacement with NM II-B or chimeric NM IIs restores a normal visceral endoderm. This finding is consistent with NM II's role in cell adhesion and also confirms an essential, isoform-independent requirement for NM II in visceral endoderm function. The knock-in mice die between E9.5 and 12.5 because of defects in placenta formation associated with abnormal angiogenesis and cell migration, revealing a unique function for NM II-A in placenta development. In vitro results further support a requirement for NM II-A in directed cell migration and focal adhesion formation. These findings demonstrate an isoform-specific role for NM II-A during these processes, making replacement by another isoform, or chimeric NM II isoforms, less successful. The failure of these substitutions is not only related to the different kinetic properties of NM II-A and II-B, but also to their subcellular localization determined by the C-terminal domain. These results highlight the functions of the N-terminal motor and C-terminal rod domains of NM II and their different roles in cell-cell and cell-matrix adhesion.
关键词：cell migration ; genetic substitution ; placenta development ; visceral endoderm formation ; chimeric myosin II
