Distinct roles for dystroglycan, beta 1 integrin and perlecan in cell surface laminin organization

Dystroglycan (DG) is a cell surface receptor for several extracellular matr ix (ECM) molecules including laminins, agrin and perlecan, Recent data indi cate that DG function is required for the formation of basement membranes i n early development and the organization of laminin on the cell surface, He re we show that DG-mediated laminin clustering on mouse embryonic stem (ES) cells is a dynamic process in which clusters are consolidated over time in to increasingly more complex structures. Utilizing various null-mutant ES c ell lines, we define roles for other molecules in this process, In beta1 in tegrin-deficient ES cells, laminin-1 binds to the cell surface, but fails t o organize into more morphologically complex structures. This result indica tes 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 per lecan in the laminin matrix assembly process. Moreover, laminin and perleca n reciprocally modulate the organization of the other on the cell surface. Taken together, the data support a model whereby DG serves as a receptor es sential for the initial binding of laminin on the cell surface, whereas bet a1 integrins and perlecan are required for laminin matrix assembly processe s after it binds to the cell.