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Mechanisms of basement membrane recognition by cell with special reference to cell adhesion-dependent signal transduction

细胞识别基底膜的机制，特别是细胞粘附依赖性信号转导

基本信息

批准号：
18370044
负责人：
SEKIGUCHI Kiyotoshi
金额：
$ 11.03万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18370044/
关键词：
basement membrane extracellular matrix laminin integrin tetraspanin nephronectin

项目摘要

Roles of individual subunit chains of laminins (i.e., alpha, beta and gamma chains) in integrin binding by laminins have been investigated. We demonstrated that the C-terminal region of the gamma1 and gamma2 chains, particularly the Glu residue at the third position from their C-termini, was critically involved in integrin recognition of laminins. Thus, the deletion of the Glu residue or the substitution of a Gln for the Glu residue abrogated the integrin binding activity of laminin isoforms containing either gamma1 or gamma2 chains. To extend the importance of the Glu residue within the gamma1 and gamma2 chains, we also demonstrated that the gamma3 chain that is shorter than other gamma chains and lacks the Glu residue was defective in binding to cognitive integrins. We also found that the C-terminal regions of the beta chains, particularly the C-terminal 22 amino acid residues, were involved in modulation of integrin binding affinities of laminins. Thus, the isoforms containing the beta2 chain was more potent than those containing the beta1 chain in binding to cognitive integrins, e.g., alpha3beta1. These results indicate that the C-terminal regions of both beta and gamma chains participate in the integrin binding by laminins. We also demonstrated that among the eight RGD-binding integrins, alpha8beta1 bound specifically to nephronectin.

层粘连蛋白的单个亚基链的作用（即，α、β和γ链）在整联蛋白与层粘连蛋白结合中的作用。我们证明，γ 1和γ 2链的C-末端区域，特别是从其C-末端的第三个位置的Glu残基，是关键参与层粘连蛋白的整合素识别。因此，Glu残基的缺失或Gln取代Glu残基消除了含有γ 1或γ 2链的层粘连蛋白亚型的整合素结合活性。为了扩展γ 1和γ 2链中Glu残基的重要性，我们还证明了比其他γ链短且缺乏Glu残基的γ 3链在与认知整合素的结合方面存在缺陷。我们还发现β链的C-末端区域，特别是C-末端22个氨基酸残基，参与调节层粘连蛋白的整合素结合亲和力。因此，含有β 2链的同种型比含有β 1链的同种型更有效地结合认知整合素，例如，α 3 β 1。这些结果表明，β和γ链的C-末端区域参与层粘连蛋白与整联蛋白的结合。我们还证明，在8个结合RGD的整合素，α 8 β 1结合特异性肾连蛋白。