CELL ADHESION-DEPENDENT REGULATION OF CELL GROWTH AND DIFFERENTIATION

细胞生长和分化的细胞粘附依赖性调节

基本信息

批准号：
06404083
负责人：
TSUKITA Shoichiro
金额：
$ 16.7万
依托单位：
KYOTO UNIVERSITY (1995)Okazaki National Research Institutes (1994)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (A)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06404083/
关键词：
cadherin radixin ezrin moesin catenin ZO-1 occuldin claudin αカテニン Z0-1 ノックアウト相同組換え ES細胞上皮細胞 ERM蛋白質 βカテニン

项目摘要

We knocked out two important genes, occludin and moesin. Here we summarized the results on moesin-null mice.ERM (ezrin/radixin/moesin) proteins are general cross-linkers between plasmamembranes and actin filaments. Since their expression is regulated in a tissue specific manner, unique function has been supposed for each of ERM proteins. On the other hand, experiments at the cellular level has suggested the functional redundancy of ERM proteins. To assess the possible overlapping functions of ERM proteins invivo, the moesin gene located on X chromosome was disrupted by gene targeting in embryonic stem cells. Hemizygous male as well as homozygous female mice for the mutation were completely devoid of moesin but were normally developed and fertile, showing no obvious histological abnormalities in all the tissues examined. In tissues of the mutant mice, moesin completely disappeared without affecting the expression levels and subcellular distribution of ezrin and radixin. Also in platelets, fibroblasts, and mast cells isolated from moesin-deficient mice, targeted disruption of 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 and radixin. These findings favor the notion that ERM proteins are functionally redundant at the cellular as well as the whole body levels.

我们淘汰了两个重要的基因，塞链蛋白和Moesin。在这里，我们总结了Moesin-null小鼠的结果。Merm（Ezrin/radixin/Moesin）蛋白是浆膜和肌动蛋白丝之间的一般交联。由于它们的表达是以组织特异性调节的，因此已经为每种ERM蛋白质所表达了独特的功能。另一方面，细胞水平的实验表明ERM蛋白的功能冗余。为了评估ERM蛋白Invivo的可能重叠功能，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。半合子雄性和纯合雌性小鼠的突变完全没有Moesin，但通常是发育且肥沃的，在所有检查的组织中没有明显的组织学异常。在突变小鼠的组织中，Moesin完全消失，而不会影响Ezrin和radixin的表达水平和亚细胞分布。同样在血小板，成纤维细胞和肥大细胞中，靶向的Moesin基因的靶向破坏不会影响其ERM依赖性功能，即，平台聚集，应激纤维/局灶性接触形成纤维细胞的形成，而无需补偿和激发度上的Mast-redricational-Rectiacty and-Rectiacty and-Readement-Rectiacty and-Rectiacty and-Reclection。这些发现有利于以下概念：ERM蛋白在细胞和整个身体水平上的功能多余。