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: 6895567
• 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 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6895567
• 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（由申请人提供）：上皮细胞组装粘合剂和 基底和细胞与细胞接触处的细胞连接处的通讯。在表皮中， 细胞连接将单个角质形成细胞整合到具有屏障和屏障的组织中 沟通功能。静止的角质形成细胞锚定在层粘连蛋白 5 上 基底膜 (BM) 通过半桥粒 (HD) 中的整合素 a6134 和整合素 粘着斑 (FA) 中的 alpha-3beta-1。细胞与细胞之间的相互作用是由 至少三种类型的细胞间连接：粘附连接（AJ）， 桥粒和间隙连接 (GJ)。连接蛋白 43 (Cx43) 是主要的 表皮中 GJ 的组成部分。静止表皮的损伤破坏 细胞连接并激活表皮细胞生长的迁移 暴露的真皮胶原蛋白和纤连蛋白，修复中层粘连蛋白 5 沉积 BM 的。生长物包含前导和后继角质形成细胞， 基于底物配体、整合素粘附、细胞信号传导和 GJ。我们已经确定了粘合剂和细胞间通讯的一种形式 表皮的连接处，并根据我们的研究提出了两种假设 发现。我们假设层粘连蛋白 5 上存在 PI3K 依赖性粘附，但并非如此 Rho 依赖性胶原蛋白粘附，促进 GJ 的组装。第二，那个细胞 静止组织中的汇合抑制胶原蛋白和纤连蛋白的粘附 但不抑制对 BM 层粘连蛋白 5 的粘附。我们建议测试这些 假设分两步进行： 1. 映射链接的组件和结构 层粘连蛋白 5 和随后的角质形成细胞中的 GJ 之间的通讯。 2. 阐明这些成分影响粘附和粘附的机制 连接通讯。这些研究将让人们了解 对调节上皮形态发生至关重要的成分和机制 发育、伤口修复和肿瘤侵袭。