ERM proteins : from cytoskeleton to signal transduction

ERM（ezrin/radixin/moesin）蛋白是质膜和肌动蛋白丝之间的一般交联剂。由于它们的表达以组织特异性方式调节，因此已经提出每种ERM蛋白具有独特的功能。另一方面，在细胞水平和体外实验表明，ERM蛋白的功能冗余。为了评估ERM蛋白在体内可能的独特功能，通过在胚胎干细胞中的基因靶向破坏位于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，并具有生育能力，在检查的任何组织中没有明显的组织学异常。在突变小鼠的组织中，膜突蛋白完全消失，而不影响ezrin和radixin的表达水平或亚细胞分布。此外，在从膜突蛋白缺陷小鼠分离的血小板、成纤维细胞和肥大细胞中，靶向破坏膜突蛋白基因并不影响它们的ERM依赖性功能，即血小板聚集、成纤维细胞的应力纤维/局灶性接触形成和肥大细胞的微绒毛形成，而不补偿性上调ezrin或radixin。这些发现支持这样的观点，即ERM蛋白在细胞和整个身体水平上都是功能冗余的

ERM (ezrin/radixin/moesin) proteins are general cross-linkers between the plasma membrane and actin filaments. Since 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 the functional redundancy of ERM proteins. 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 moesindeficient mice, targeted disruption of the moesin gene did not affect their ERM-dependent functions, i.e. platelet aggregation, stress fiber/focal contact formation offibroblasts ; 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