STRUCTURAL ANALYSES AND FUNCTIONS OF RECEPTORS FOR CELL ADHESION PROTEINS

细胞似乎与结构和调节分子相互作用， 细胞外基质通过特定的受体。 我们已经分析 两种主要糖蛋白纤连蛋白和胶原蛋白的假定受体。 一种膜糖蛋白复合物，由以下三种组分组成： 大约140，000道尔顿的分子量显示出与 细胞外纤维连接蛋白和细胞内α-辅肌动蛋白 微丝束 针对该复合物的单克隆抗体阻断了 细胞与纤连蛋白的粘附，单独的底物附着抗体可以 模拟纤连蛋白介导的扩散。 这个假定的组成部分 纤连蛋白受体复合物被分离，并显示出三种不同的 酸性唾液酸糖蛋白非共价结合成寡聚体， 复杂. 其他研究表明神经节苷脂参与了 细胞外纤维连接蛋白原纤维，并显示这些定位 脂质在其附着于细胞表面的位点处。 可能 通过胶原蛋白的占据调节纤连蛋白受体功能 受体进行了探索。 细胞与胶原蛋白或其α 1（I）的孵育 链被发现抑制纤连蛋白受体的特定子集 以非竞争性的方式运作。 细胞铺展和吞噬作用 抑制，而直接结合和细胞附着到纤连蛋白包被的 底物不受影响。 我们未来的目标是分析 纤维连接蛋白和胶原蛋白受体的结构和功能。 将使用单克隆和多克隆抗体， 蛋白水解切割以限定各自的结构和功能结构域。 转化后其分布和磷酸化的改变 并建立热休克。 重构实验和 对生物功能所需的其他分子的分析应该提供一个 进一步了解其作用机制。

Cells appear to interact with structural and regulatory molecules in the extracellular matrix by means of specific receptors. We have analyzed putative receptors for two major glycoproteins, fibronectin and collagen. A membrane glycoprotein complex consisting of three components of approximately 140,000 daltons each was shown to co-localize partially with extracellular fibronectin and with intracellular Alpha-actinin in microfilament bundles. Monoclonal antibodies against this complex blocked cell adhesion to fibronectin, and substrate-attached antibody alone could mimic fibronectin-mediated spreading. The components of this putative fibronectin receptor complex were isolated and shown to be three distinct acidic sialoglycoproteins associated noncovalently into an olgomeric complex. Other studies implicated gangliosides in cellular organization of extracellular fibronectin fibrils, and showed a localization of these lipids at sites of their attachment to the cell surface. Possible modulation of fibronectin receptor function by occupancy of the collagen receptor was explored. Incubation of cells with collagen or its Alpha1(I) chain was found to inhibit a specific subset of fibronectin receptor functions in non-competitive fashion. Cell spreading and phagycytosis were inhibited, while direct binding and cell attachment to fibronectin-coated substrates were unaffected. Our future objectives will be to analyze the structures and functions of the receptors for fibronectin and collagen. Monoclonal and polyclonal antibodies will be used with controlled proteolytic cleavage to define structural and functional domains of each. Alterations in their distribution and phosphorylation after transformation and heat shock will be established. Reconstitution experiments and analyses of other molecules needed for biological function should provide a further understanding of their mechanisms of action.