RECOGNITION MOLECULES MYELIN-ASSOCIATED GLYCOPROTEIN AND TENASCIN-C INHIBIT INTEGRIN-MEDIATED ADHESION OF NEURAL CELLS TO COLLAGEN

Because of the importance of collagens in mediating cell-substrate int eractions and the association of collagens with neural recognition mol ecules in the peripheral nervous system, the ability of neural recogni tion molecules to modify the substrate properties of collagens, in par ticular collagen type I, for cell adhesion was determined. Two cell li nes, the N2A neuroblastoma and PC12 pheochromocytoma, were investigate d for their capacity to adhere to different collagen types in the abse nce or presence of several neural recognition molecules, Adhesion of N 2A or PC12 cells and membrane vesicles from PC12 cells to collagen typ e I was reduced when the collagen had been preincubated prior to its a pplication as substrate with the extracellular domain of myelin-associ ated glycoprotein (s-MAG) or, as control, fibroblast tenascin-C (F-ten ascin). In mixture with other collagen types, s-MAG was only able to r educe the adhesiveness of collagen types III and V, but not of collage n types II and IV, F-tenascin reduced the adhesiveness of all collagen types tested, In contrast to F-tenascin, s-MAG had to be present duri ng fibrillogenesis to exert its effect, indicating that it must be coa ssembled into the collagen fibril to block the cell binding site, Cell adhesion to collagen type I was dependent on Mg2+ or Mn2+ and inhibit ed by a monoclonal antibody to the or, integrin subunit, The combined observations indicate that s-MAG and F-tenascin interfere with cell bi nding, most probably by modifying the integrin binding site, and that the two molecules act by different mechanisms, both leading to reducti on of adhesion. (C) 1995 Wiley-Liss, Inc.