Regulation of cell polarity and tight junction formation in vertebrate epithelial and endothelial cells by cell adhesion receptors

细胞粘附受体调节脊椎动物上皮细胞和内皮细胞的细胞极性和紧密连接形成

• 批准号: 5332586
• 负责人: Professor Dr. Klaus Thomas Ebnet
• 金额: --
• 依托单位: Institut für Medizinische Biochemie
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2001
• 资助国家: 德国
• 起止时间: 2000-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5332586?language=en
• 关键词: Regulation; cell; polarity; tight; junction

Until recently, little was known about the molecules regulating the formation of tight junctions (TJ) and membrane polarity in vertebrate epithelial and endothelial cells. The recent discovery of a multicomponent signalling complex consisting of PDZ domain-containing scaffolding proteins (PAR-3, PAR-6) and signal transducing proteins (aPKC, Cdc42) has attracted much attention in the field of cell polarity. This complex is conserved through evolution and seems to be required for the formation and/or maintenance of tight junctions in epithelial cells. With JAM-1 we have identified the first transmembrane component in TJs which associates with PAR-3. Our studies aim at a more detailed understanding of the function of JAM-1 in the formation of TJs. The specific aims are: (1) to analyze if the association of PAR-3 with JAM is required for a) the recruitment of PAR-3 to intercellular contacts and b) the formation of tight junctions in epithelial cells; (2) to analyze protein complexes involving JAMs and members of the ZO family of TJ proteins (ZO-1, ZO-2, and ZO-3); and (3) to analyze if Hepatocyte Growth Factor affects TJ integrity by acting on the TJ localization of JAM-1.

直到最近，人们对调节脊椎动物上皮细胞和内皮细胞中紧密连接（TJ）形成和膜极性的分子知之甚少。最近发现的由含有PDZ结构域的支架蛋白（PAR-3、PAR-6）和信号转导蛋白（aPKC、Cdc42）组成的多组分信号复合物引起了细胞极性领域的广泛关注。该复合物在进化过程中是保守的，并且似乎是上皮细胞中紧密连接的形成和/或维持所必需的。通过 JAM-1，我们确定了 TJ 中与 PAR-3 相关的第一个跨膜成分。我们的研究旨在更详细地了解 JAM-1 在 TJ 形成中的功能。具体目标是：(1) 分析 PAR-3 与 JAM 的关联是否是 a) PAR-3 募集到细胞间接触和 b) 上皮细胞中紧密连接形成所必需的； (2) 分析涉及 JAM 和 TJ 蛋白 ZO 家族成员（ZO-1、ZO-2 和 ZO-3）的蛋白复合物； (3) 分析肝细胞生长因子是否通过作用于 JAM-1 的 TJ 定位来影响 TJ 完整性。