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

• 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

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.

我们敲除了两个重要的基因，闭合蛋白和膜突蛋白。ERM（ezrin/radixin/moesin）蛋白是质膜和肌动蛋白丝之间的一种普遍的交联蛋白。由于它们的表达以组织特异性方式调节，因此推测每个ERM蛋白具有独特的功能。另一方面，在细胞水平的实验表明，ERM蛋白的功能冗余。为了评估ERM蛋白在体内可能的重叠功能，通过基因打靶在胚胎干细胞中破坏位于X染色体上的膜突蛋白基因。突变的半合子雄性以及纯合子雌性小鼠完全缺乏膜突蛋白，但发育正常且可生育，在检查的所有组织中均未显示出明显的组织学异常。在突变小鼠的组织中，膜突蛋白完全消失，而不影响ezrin和radixin的表达水平和亚细胞分布。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，膜突蛋白基因的靶向破坏不影响它们的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和radixin。这些发现支持这样的观点，即ERM蛋白在细胞和全身水平上都是功能冗余的。

项目成果

Yonemura, S., Itoh, M., Nagafuchi, A., and Tsukita, Sh.: "Cell-to-cell adherens junction formation and actin filament organization : Similarities and difference between non-polarized fibroblasts and polarized epithelial cells." J.Cell Sci.108. 127-142 (19

Yonemura, S.、Itoh, M.、Nagafuchi, A. 和 Tsukita, Sh.：“细胞间粘附连接形成和肌动蛋白丝组织：非极化成纤维细胞和极化上皮细胞之间的异同。”

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武田，H.等。

Takeuchi, K., Kawashima, A., Nagafuchi, A., and Tsukita, Sh.: "Structural diversity of band 4.1 superfamily members." J.Cell Sci.107. 1921-1928 (1994)

Takeuchi, K.、Kawashima, A.、Nagafuchi, A. 和 Tsukita, Sh.：“乐队 4.1 超家族成员的结构多样性。”

Nagafuchi, A., Ishihara, S., and Tsukita, Sh.: "The roles of catenins in the cadherin-mediated cell adhesion : Functional analysis of E-cadherin alpha catenin fusion molecules." J.Cell Biol.127. 235-245 (1994)

Nagafuchi, A.、Ishihara, S. 和 Tsukita, Sh.：“连环蛋白在钙粘蛋白介导的细胞粘附中的作用：E-钙粘蛋白 α 连环蛋白融合分子的功能分析。”

Nagafuchi,A.: "The nervous tissue-specific loss of the expression of alpha-catenin,the 102kD cadherin-associated protein,during development." Develop,Growth & Differ.36. 59-71 (1994)

Nagafuchi,A.：“在发育过程中，神经组织特异性地丧失 α-连环蛋白（102kD 钙粘蛋白相关蛋白）的表达。”