Doi Y, Itoh M, Yonemura S, Ishihara S, Takano H, Noda T, Tsukita S
Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606, Japan.
J Biol Chem. 1999 Jan 22;274(4):2315-21. doi: 10.1074/jbc.274.4.2315.
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.
埃兹蛋白/根蛋白/膜突蛋白（ERM）是质膜与肌动蛋白丝之间的通用交联蛋白。由于它们的表达以组织特异性方式受到调控，因此有人提出每种ERM蛋白都具有独特的功能。另一方面，细胞水平和体外实验表明它们具有功能冗余性。为了评估ERM蛋白在体内可能具有的独特功能，通过在胚胎干细胞中进行基因靶向，破坏了位于X染色体上的膜突蛋白基因。突变的半合子雄性小鼠以及纯合子雌性小鼠完全缺乏膜突蛋白，但发育正常且可育，在所检查的任何组织中均无明显的组织学异常。在突变小鼠的组织中，膜突蛋白完全消失，而不影响埃兹蛋白和根蛋白的表达水平或亚细胞分布。此外，在从缺乏膜突蛋白的小鼠中分离出的血小板、成纤维细胞和肥大细胞中，膜突蛋白基因的靶向破坏并不影响它们依赖ERM的功能，即血小板聚集、成纤维细胞应力纤维/粘着斑形成以及肥大细胞微绒毛形成，且埃兹蛋白或根蛋白没有代偿性上调。这些发现支持了ERM蛋白在细胞水平以及全身水平上功能冗余的观点。
