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交联剂。由于ERM蛋白的表达受到组织特异性的调控，因此每个ERM蛋白都被认为具有独特的功能。另一方面，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，我们在胚胎干细胞中通过基因靶向破坏了位于X染色体上的moesin基因。突变半合子的雄性小鼠和纯合子的雌性小鼠完全缺乏moesin，但发育正常且可生育，所检查的任何组织均无明显组织学异常。突变小鼠的组织中，moesin完全消失，不影响ezrin和radixin的表达水平和亚细胞分布。此外，在从moesin缺乏小鼠中分离的血小板、成纤维细胞和肥大细胞中，靶向破坏moesin基因并不影响其erm依赖性功能，即血小板聚集、应激纤维/局灶接触形成成纤维细胞；肥大细胞的微绒毛形成，没有代偿性上调ezrin或radixin。这些发现支持ERM蛋白在细胞和整个身体水平上功能冗余的观点

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