CELL ADHESION IN TISSUE MORPHOGENESIS

我们的长期目标是确定涉及的受体和机制 在与细胞外基质(ECM)和其他细胞的相互作用中 以及这些再捕获器如何在分化和 形态发生过程。我们在结构和功能上定义了三个 相关的ECM受体(ECMR)II、VI和I，每个140 kDa，介导 间充质细胞与胶原、纤维连接蛋白和 分别是胶原/纤维连接蛋白/层粘连蛋白，我们还定义了第四种 90 kDa的eCMR与胶原蛋白结合，称为胶原蛋白受体III (CRIII)，它在大多数有核细胞中表达。中环填海第三期工程与 蛋白多糖(GAG200)，与Hermes-1和Mel 14同源 抗原，淋巴细胞与内皮细胞黏附的介体。因此，中环填海第三期工程可 在许多细胞群中调节细胞间的黏附以及相互作用 使用ECM。ECMR也由上皮细胞表达，通常由ECM表达 提示ECMR的其他可能功能的配体。这 提案将利用生化和免疫学技术进行评估； 1.CRIII在介导细胞间黏附中的作用 多个细胞群。(A)发展化验方法，以检查 CRIII在细胞-细胞黏附中的作用。(B)可能的配基鉴定 GAG200或胶原，用于参与细胞间黏附的CRIII。II.THE ECMRS在上皮细胞和其他细胞定位于组织中的功能作用 结构域(A)在正常组织和恶性肿瘤组织中的定位 与ECM组件的关系。(B)制定评估作用的分析方法 上皮内ECM-ECMB相互作用的研究。(C)ECM-eCMR的作用 上皮细胞特性(极性、 迁移、分化)。

Our long term goals are to determine the receptors and mechanisms involved in cell interactions with the extracellular matrix (ECM) and other cells and how these recaptors function cooperatively in differentiation and morphogenic processes. We have defined three structurally and functionally related ECM receptors (ECMRs), II, VI and I, of 140 kDa each that mediate mesenchymal cell adhesion to collagen, fibronectin and collagen/fibronectin/laminin, respectively, We have also defined a fourth ECMR of 90 kDa, that binds to collagen, termed collagen receptor III (CRIII), that is expressed in most nucleated cells. CRIII interacts with a proteoglycan (GAG200) and is homologous to the Hermes-1 and Mel 14 antigens, mediators of lymphocyteendothelial cell adhesion. Thus, CRIII may mediate cell-cell adhesion in many cell populations as well as interact with the ECM. The ECMR are also expressed by epithelial cells and often ECM ligand suggesting additional possible functions for the ECMRs. This proposal will utilize biochemical and immunological techniques to evaluate; 1. THE FUNCTIONAL ROLE OF CRIII IN MEDIATING INTERCELLULAR ADHESION IN MULTIPLE CELL POPULATIONS. (A) Development of assays to examine the role of CRIII in cell-cell adhesion. (B) Identification of a ligand, possible GAG200 or collagen, for CRIII involved in cell-cell adhesion. II.THE FUNCTIONAL ROLE OF ECMRS IN LOCALIZING EPITHELIAL AND OTHER CELLS TO TISSUE DOMAINS (A) Localization of ECMRs in normal and malignant tissue in relation to ECM components. (B) Development of assays to evaluate the role of ECM-ECMB interactions in epithelium. (C) The role of ECM-ECMR interactions in expression of epithelial cell characteristics (polarity, migration, differentiation).