A Novel Cell-Cell Adhesion System at Adherens Junction

粘附连接处的新型细胞-细胞粘附系统

• 批准号: 12680697
• 负责人: MANDAI Kenji
• 金额: $ 2.37万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12680697/
• 关键词: Cell-Cell Adhesion; Adherens Junction; Tight Junction; Nectin; Afadin; Cadherin-Catenin; ZO-1; mLin-7; 細胞接着; ZO-1; 細胞生物学

We have identified a novel cell-cell adhesion system, which consists of nectin and afadin. Nectin is an immunoglobulin-like adhesion molecule and afadin is a nectin- and actin filament-binding protein.Nectin and afadin are ubiquitously expressed and localized at adherens junctions. The nectin-afadin system plays an important role in the proper organization of adherens and tight junctions. In the present research project, we have studied the functions and mode of action of the nectin-afadin system.1. Organization of adherens and tight junctions. We have shown that the complex of cadherin and β-catenin is recruited to the nectin-based cell-cell junction through afadin and α-catenin and that ZO-1 is recruited to the nectin-based cell-cell junction through afadin. These results suggest that the nectin-afadin system organizes adherens and tight junctions through the recruitment of cadherin and ZO-1. Moreover, using a human signet ring cell gastric cancer cell line, HSC-39 cells, we have shown that the nectin-afadin and cadherin-catenin systems cooperatively form adherens junctions.2. Localization of mLin-7 at adherens junction. We have shown that mLin-7, the mammalian homologue of C. elegans LIN-7, localizes at adherens junctions through the nectin-afadin system. The function of mammalian mLin-7 is unknown, while LIN-7 is involved in the proper localization of LET-23 receptor tyrosine kinase in C. elegans. These results suggest that the nectin-afadin system determines the localization of a certain growth factor receptor.

我们已经确定了一种新的细胞-细胞粘附系统，它由nectin和afadin。Nectin是一种免疫球蛋白样粘附分子，afadin是一种与Nectin和肌动蛋白结合的蛋白质，它们广泛表达并定位于粘附连接处。nectin-afadin系统在粘附和紧密连接的正确组织中起重要作用。在本研究项目中，我们研究了nectin-afadin系统的功能和作用方式.粘附和紧密连接的组织。我们已经证明，钙粘蛋白和β-连环蛋白的复合物通过afadin和α-连环蛋白被募集到基于连接蛋白的细胞-细胞连接，ZO-1通过afadin被募集到基于连接蛋白的细胞-细胞连接。这些结果表明，nectin-afadin系统通过募集钙粘蛋白和ZO-1来组织粘附和紧密连接。此外，利用人印戒细胞胃癌细胞系HSC-39细胞，我们已经证明了nectin-afadin和cadherin-catenin系统协同形成粘附连接. mLin-7在粘附连接处的定位。我们已经证明，mLin-7，哺乳动物同源的C。elegans LIN-7通过nectin-afadin系统定位于粘附连接处。哺乳动物mLin-7的功能尚不清楚，而LIN-7参与了C.优美的这些结果表明，nectin-afadin系统决定了某种生长因子受体的定位。

项目成果

Peng, Y.-F.: "Ankycorbin : a novel actin cytoskeleton-associated protein"Genes Cells. 5・12. 1001-1008 (2000)

Peng，Y.-F.：“Ankycorbin：一种新型肌动蛋白细胞骨架相关蛋白”，Genes Cells 5·1008（2000）。

Yokoyama, S.: "α-Catenin-independent recruitment of ZO-1 to nectin-based cell-cell adhesion sites through afadin"Mol. Biol. Cell. 12. 1595-1609 (2001)

Yokoyama，S.：“通过 afadin 将 ZO-1 独立地募集至基于连接蛋白的细胞间粘附位点”Mol Biol。

Ono, Y.: "Two actions of frabin : direct activation of Cdc4-2 and indirect activation 0f Rac"Oncogene. 19. 3050-3058 (2000)

Ono, Y.：“frabin 的两种作用：直接激活 Cdc4-2 和间接激活 0f Rac”癌基因。

Yokoyama,S.: "α-Catenin-independent Recruitment of ZO-1 to Nectin-based Cell-Cell Adhesion Sites through Afadin."Mol.Biol.Cell. (In press). (2001)

Yokoyama, S.：“通过 Afadin 将 ZO-1 独立于 α-连环蛋白募集到基于 Nectin 的细胞-细胞粘附位点”。Mol.Biol.Cell（出版中）。

Peng, Y. -F.: "Restoration of E-cadherin-based cell-cell adhesion by over-expression of nectin in HSC-39 celis, a human signet ring cell gastric cancer cell line"Oncogene. (in press). (2002)

Peng，Y.-F.：“通过在人印戒细胞胃癌细胞系 HSC-39 细胞中过度表达 nectin 来恢复基于 E-钙粘蛋白的细胞间粘附”Oncogene。