Normal development of mice and unimpaired cell adhesion cell motility actin-based cytoskeleton without compensatory up-regulation of ezrin or radixin in moesin gene knockout
Normal development of mice and unimpaired cell adhesion cell motility actin-based cytoskeleton without compensatory up-regulation of ezrin or radixin in moesin gene knockout
复制标题
DOI：
10.1074/jbc.274.4.2315
复制
发表时间：
1999-01-22
影响因子：
4.8
通讯作者：
Tsukita, S
中科院分区：
文献类型：
--
作者：
Doi, Y;Itoh, M;Tsukita, S
Ezrin/radixin/Moesin（ERM）蛋白是质膜和肌动蛋白丝之间的一般交联。由于它们的表达以组织特异性方式调节，因此已提出每个ERM蛋白具有独特的功能。另一方面，在细胞水平和体外的实验表明它们的功能冗余。为了评估ERM蛋白在体内的可能独特功能，位于X染色体上的Moesin基因被胚胎干细胞中的基因靶向破坏。雄性小鼠半合子进行突变以及纯合雌性完全没有Moesin，但正常发育并且肥沃，在任何研究的组织中均无明显的组织学异常。在突变小鼠的组织中，Moesin完全消失，而不会影响Ezrin和radixin的表达水平或亚细胞分布，同样在血小板，成纤维细胞和肥大细胞中，从Moesin缺陷型小鼠中分离出来，靶向Moesin Gene的靶向破坏也不影响Moesin Gene的破坏。它们的ERM依赖性功能，即血小板聚集，应力纤维/局灶性接触形成肥大细胞的成纤维细胞和微循环形成，没有ezrin或radixin的代偿上调，这些发现有利于ERM蛋白在细胞和整个身体水平上功能上冗余的概念。
Ezrin/radixin/moesin (ERM) proteins are general cross-linkers between the plasma membrane and actin filaments. Because their expression is regulated in a tissue-specific manner, each ERM protein has been proposed to have unique functions. On the other hand, experiments at the cellular level and in vitro have suggested their functional redundancy. To assess the possible unique functions of ERM proteins in vivo, the moesin gene located on the X chromosome was disrupted by gene targeting in embryonic stem cells. Male mice hemizygous for the mutation as well as homozygous females were completely devoid of moesin but developed normally and were fertile, with no obvious histological abnormalities in any of the tissues examined. In the tissues of the mutant mice, moesin completely disappeared without affecting the expression levels or subcellular distribution of ezrin and radixin, Also, in platelets, fibroblasts, and mast cells isolated from moesin-deficient mice, targeted disruption of the moesin gene did not affect their ERM-dependent functions, i.e. platelet aggregation, stress fiber/focal contact formation of fibroblasts, and microvillar formation of mast cells, without compensatory up-regulation of ezrin or radixin, These findings favor the notion that ERM proteins are functionally redundant at the cellular as well as the whole body level.