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Molecular links between vector transport machinery and cell adhesion machinery

载体运输机械和细胞粘附机械之间的分子联系

基本信息

批准号：
12144203
负责人：
HATA Yutaka
金额：
$ 32.64万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2004
项目状态：
已结题

项目摘要

In this project, we have analyzed the molecular links between vector transport machinery and cell adhesion machinery. Our primary focus is on membrane-associated proteins that interact directly or indirectly with cell adhesion molecules.We identified novel membrane-associated proteins including PAPIN, ankycorbin, and carom. PAPIN is a multi-PDZ protein and presumably a scaffold protein. Both of ankycorbin and carom indirectly interact with actin. Interestingly, carom interacts with MAGI-1, a tight junction-associated protein, before cell junctions become mature but it comes to bind to CASK, a different membrane-associated protein, in fully polarized epithelial cells. We also clarified how membrane-associated proteins are targeted to epithelial junctions. MAGI-1 is recruited to the lateral membranes through the interaction with beta-catenin. PAPIN and ERBIN interact with p0071, a member of catenin family proteins, but their subcellular localizations are independent of these interactions … More . Likewise, Lin-7, a beta-catenin-interactor, is recruited to the lateral membranes by a cell adhesion molecule, nectin, and its associated protein, afadin, but not by beta-catenin. We also discovered a novel cell adhesion molecule that binds to MAGI-1 and named it JAM4. JAM4 and MAGI-1 co-operate to regulate the intercellular permeability. JAM4 enhances hepatocyte growth factor-mediated signaling putatively by activating Rac. At synapses, a neuronal isoform of MAGI-1 named S-SCAM, which is recruited by beta-catenin to cadherin-based adhesion sites, subsequently induces another cell adhesion mediated by neuroligin and triggers the remodeling of actin cytoskeleton. Similarly, in epithelial cells, nectin induces the cadherin-based adhesion via afadin and the accumulation ofJAM1 that is a component of tight junctions. Moreover, we have found that MAGI-1 links JAM4 and nephrin in kidney glomeruli. All these findings indicate that membrane-associated proteins are important to link different categories of cell adhesion molecules. Finally, we have obtained four novel proteins binding to microtubules. Less

在这个项目中，我们分析了载体转运机制和细胞粘附机制之间的分子联系。我们主要关注与细胞粘附分子直接或间接相互作用的膜相关蛋白，我们鉴定了新的膜相关蛋白，包括PAPIN、ankycorbin和carom。PAPIN是一种多PDZ蛋白，可能是一种支架蛋白。ankycorbin和carom都与肌动蛋白间接相互作用。有趣的是，在细胞连接成熟之前，carom与MAGI-1（一种紧密连接相关蛋白）相互作用，但在完全极化的上皮细胞中，它与CASK（一种不同的膜相关蛋白）结合。我们还阐明了膜相关蛋白如何靶向上皮连接。MAGI-1通过与β-连环蛋白的相互作用被募集到侧膜。PAPIN和ERBIN与p0071相互作用，p0071是连环蛋白家族蛋白质的成员，但它们的亚细胞定位不依赖于这些相互作用 ...更多信息 .同样，β-连环蛋白相互作用因子Lin-7被细胞粘附分子nectin及其相关蛋白afadin募集到侧膜，但不被β-连环蛋白募集。我们还发现了一种与MAGI-1结合的新型细胞粘附分子，并将其命名为JAM 4。JAM 4和MAGI-1协同调节细胞间通透性。JAM 4通过激活Rac增强肝细胞生长因子介导的信号转导。在突触处，MAGI-1的神经元同种型S-SCAM被β-连环蛋白募集到基于钙粘蛋白的粘附位点，随后诱导由神经连接蛋白介导的另一种细胞粘附并触发肌动蛋白细胞骨架的重塑。类似地，在上皮细胞中，nectin通过afadin和作为紧密连接组分的JAM 1的积累诱导基于钙粘蛋白的粘附。此外，我们已经发现MAGI-1在肾小球中连接JAM 4和nephrin。所有这些发现表明，膜相关蛋白是重要的连接不同类别的细胞粘附分子。最后，我们获得了四个新的蛋白质结合微管。少

项目成果

期刊论文数量（164）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Synaptic localization of membrane-associated guanylate kinase-interacting protein mediated by the pleckstrin homology domain

DOI：
10.1046/j.1460-9568.2002.01987.x
发表时间：
2002-05-01
期刊：
EUROPEAN JOURNAL OF NEUROSCIENCE
影响因子：
3.4
作者：
Iida, J;Nishimura, W;Hata, Y
通讯作者：
Hata, Y

Contacts between the commissural axons and the floor plate cells are mediated by nectins

DOI：
10.1016/j.ydbio.2004.05.034
发表时间：
2004-09-15
期刊：
DEVELOPMENTAL BIOLOGY
影响因子：
2.7
作者：
Okabe, N;Shimizu, K;Takai, Y
通讯作者：
Takai, Y

Nectin and afadin: novel organizers of intercellular junctions

DOI：
10.1242/jcs.00167
发表时间：
2003-01-01
期刊：
JOURNAL OF CELL SCIENCE
影响因子：
4
作者：
Takai, Y;Nakanishi, H
通讯作者：
Nakanishi, H

Synaptic scaffolding molecule is involved in the synaptic clustering of neuroligin

DOI：
10.1016/j.mcn.2004.08.006
发表时间：
2004-12-01
期刊：
MOLECULAR AND CELLULAR NEUROSCIENCE
影响因子：
3.5
作者：
Lida, J;Hirabayashi, S;Hata, Y
通讯作者：
Hata, Y

Localization of p0071-interacting proteins, plakophilin-related armadillo-repeat protein-interacting protein and ERBIN, in epithelial cells.

p0071 相互作用蛋白、plakophilin 相关犰狳重复蛋白相互作用蛋白和 ERBIN 在上皮细胞中的定位。

DOI：
发表时间：
2002
期刊：
Oncogene 21
影响因子：
0
作者：
Takai Y;Nakanishi H;Nishimura W et al.;Iida J et al.;Yao I et al.;Ohtsuka T et al.;Kim Y et al.;Momose Y et al.;Yamamoto Y et al.;Peng Y-E et al.;Ozaki-Kuroda K et al.;Hirabayashi S et al.;Ohno H et al.
通讯作者：
Ohno H et al.