Distinct roles for dystroglycan, beta1 integrin and perlecan in cell surface laminin organization.
Distinct roles for dystroglycan, beta1 integrin and perlecan in cell surface laminin organization.
复制标题
DOI：
--
复制
发表时间：
2001-03
影响因子：
4
通讯作者：
Michael D. Henry;Jakob S. Satz;C. Brakebusch;M. Costell;E. Gustafsson;R. Fässler;K. Campbell
中科院分区：
文献类型：
--
作者：
Michael D. Henry;Jakob S. Satz;C. Brakebusch;M. Costell;E. Gustafsson;R. Fässler;K. Campbell
肌营养不良聚糖（DG）是包括层粘连蛋白、聚集蛋白和串珠素在内的几种细胞外基质（ECM）分子的细胞表面受体。最近的数据表明，DG的功能是需要在早期发展和组织层粘连蛋白的细胞表面上的基底膜的形成。在这里，我们表明，DG介导的层粘连蛋白集群小鼠胚胎干细胞（ES）是一个动态的过程中，集群巩固随着时间的推移，越来越复杂的结构。利用各种空突变的ES细胞系，我们定义在这个过程中的其他分子的作用。在β 1整合素缺陷的ES细胞中，层粘连蛋白-1结合到细胞表面，但不能组织成形态上更复杂的结构。这一结果表明，在细胞表面介导的层粘连蛋白组装过程中，DG发挥作用后需要β 1整合素功能。在串珠素缺陷的ES细胞中，复合层粘连蛋白-1结构的形成是有缺陷的，这暗示串珠素参与层粘连蛋白基质组装过程。此外，层粘连蛋白和串珠素调节细胞表面上另一个的组织。两者合计，数据支持一个模型，其中DG作为一个重要的层粘连蛋白在细胞表面上的初始结合的受体，而β 1整合素和串珠素是必需的层粘连蛋白基质组装过程后，它结合到细胞。
Dystroglycan (DG) is a cell surface receptor for several extracellular matrix (ECM) molecules including laminins, agrin and perlecan. Recent data indicate that DG function is required for the formation of basement membranes in early development and the organization of laminin on the cell surface. Here we show that DG-mediated laminin clustering on mouse embryonic stem (ES) cells is a dynamic process in which clusters are consolidated over time into increasingly more complex structures. Utilizing various null-mutant ES cell lines, we define roles for other molecules in this process. In beta1 integrin-deficient ES cells, laminin-1 binds to the cell surface, but fails to organize into more morphologically complex structures. This result indicates that beta1 integrin function is required after DG function in the cell surface-mediated laminin assembly process. In perlecan-deficient ES cells, the formation of complex laminin-1 structures is defective, implicating perlecan in the laminin matrix assembly process. Moreover, laminin and perlecan reciprocally modulate the organization of the other on the cell surface. Taken together, the data support a model whereby DG serves as a receptor essential for the initial binding of laminin on the cell surface, whereas beta1 integrins and perlecan are required for laminin matrix assembly processes after it binds to the cell.