Communication Between Laminin 5 and Gap Junctions

描述(申请人提供)：上皮细胞组装粘附剂和 在衬底和细胞-细胞接触处进行细胞连接的通信。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。静止期角质形成细胞与层粘连蛋白5结合 基底膜(BM)通过半桥粒(HD)中的整合素a6134和整合素 局灶性粘连(FAs)中的α-3β-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：粘连连接(AJ)， 桥粒和缝隙连接(GJS)。连接蛋白43(Cx43)是主要的 表皮中GJS的成分。静止性表皮的损伤破坏 细胞连接并激活表皮细胞突起的迁移 暴露的真皮胶原和纤维连接蛋白与层粘连蛋白5在修复中的沉积 BM的。突起包含引导和跟随角质形成细胞， 根据底物配体、整合素黏附、细胞信号和 GJS。我们已经确定了粘合剂和细胞之间的一种通信形式--细胞 并根据我们的研究提出了两个假说 调查结果。我们假设PI3K依赖于层粘连蛋白5的黏附，但不是 依赖Rho的胶原蛋白黏附，促进GJS的组装。第二，那个细胞 静止组织中的融合抑制与胶原和纤维连接蛋白的黏附 但不抑制与BM层粘连蛋白5的黏附。我们建议测试这些 假设分为两个步骤：1.映射链接的组件和结构 层粘连蛋白5和GJS在下列角质形成细胞中的通讯。2. 阐明这些成分用来影响粘附力和 交汇点通信。这些研究将提供对 调控上皮细胞形态发生的关键成分和机制 发展、伤口修复和肿瘤侵袭。

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.