Communication Between Laminin 5 and Gap Junctions

层粘连蛋白 5 和间隙连接之间的通讯

• 批准号: 6632738
• 负责人: WILLIAM G. CARTER
• 金额: $ 41.09万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-15 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6632738
• 关键词: basement membrane; cell cell interaction; cell growth regulation; cell population study; collagen; gap junctions; genetically modified animals; human tissue; integrins; intercellular connection; keratinocyte; laboratory mouse; laminin; microarray technology; phosphatidylinositol 3 kinase; protein binding; skin; skin transplantation; tissue /cell culture; wound healing

DESCRIPTION (provided by applicant): Epithelial cells assemble adhesive and communicating cell junctions at substrate and cell-cell contacts. In epidermis, cell junctions integrate individual keratinocytes into tissue with barrier and communicating functions. Quiescent keratinocytes anchor to laminin 5 in the basement membrane (BM) via integrin a6134 in hemidesmosomes (HD) and integrin alpha-3beta-1 in focal adhesions (FAs). Cell-cell interactions are mediated by at least three types of intercellular junctions: adherens junctions (AJs), desmosomes and gap junctions (GJs). Connexin 43 (Cx43) is the predominant constituent of GJs in the epidermis. Wounding of quiescent epidermis disrupts cell junctions and activates migration of an epidermal cell outgrowth over exposed dermal collagen and fibronectin with deposition of laminin 5 in repair of the BM. The outgrowth contains both leading and following keratinocytes that are distinct based on substrate ligands, integrin adhesion, cell signaling, and GJs. We have identified a form of communication between adhesive and cell-cell junctions in the epidermis and have suggested two hypotheses based on our findings. We hypothesize that PI3K-dependent adhesion on laminin 5, but not Rho-dependent adhesion on collagen, promotes assembly of GJs. Second, that cell confluence in quiescent tissues inhibits adhesion to collagen and fibronectin but does not inhibit adhesion to BM laminin 5. We propose to test these hypotheses in two steps: 1. Map components and structures that link communication between laminin 5 and GJs in the following keratinocytes. 2. Elucidate the mechanisms that these components utilize to affect adhesion and junctional communication. These studies will provide an understanding of components and mechanisms critical for regulating epithelial morphogenesis in development, wound repair and tumor invasion.

描述（由申请方提供）：上皮细胞组装粘合剂， 在基底和细胞-细胞接触处连通细胞连接。在表皮中， 细胞连接将单个角质形成细胞整合到具有屏障的组织中， 沟通功能。静止的角质形成细胞锚于层粘连蛋白5， 基底膜（BM）通过半桥粒（HD）中的整合素α 6134和整合素α 6134介导 局灶性粘连（FA）中的α-3 β-1。细胞间的相互作用是由 至少三种类型的细胞间连接：粘附连接（AJs）， 桥粒和间隙连接（GJ）。连接蛋白43（Cx43）是主要的 表皮中的GJ成分。静止表皮的创伤破坏了 细胞连接并激活表皮细胞的迁移， 暴露的真皮胶原蛋白和纤维连接蛋白，层粘连蛋白5在修复中沉积 的BM。生长物包含前导和后续角质形成细胞， 基于底物配体、整合素粘附、细胞信号传导和 GJ我们已经确定了一种形式的沟通之间的粘附和细胞细胞 在表皮的交界处，并提出了两个假设的基础上，我们 调查结果。我们假设PI 3 K依赖的层粘连蛋白5的粘附，而不是 Rho依赖性粘附在胶原蛋白上，促进GJ的组装。第二，这个细胞 静止组织中的汇合抑制与胶原和纤连蛋白的粘附 但不抑制与BM层粘连蛋白5的粘附。我们建议测试这些 假设分两步：1.地图组件和结构链接 在以下角质形成细胞中层粘连蛋白5和GJ之间的通讯。2. 阐明这些成分影响粘附力的机制， 连接通信这些研究将有助于了解 调节上皮形态发生的关键成分和机制 发育、伤口修复和肿瘤侵袭。