Growth cone migration across extracellular matrix components depends on integrin, but migration across glioma cells does not.

To promote neurite elongation, nerve growth cones must adhere to other surfaces. A complex of integral membrane glycoproteins mediates cell binding to the extracellular glycoproteins fibronectin and laminin (Horwitz et al., J Cell Biol 101:2134-2144, 1985). The receptor complex, named integrin, binds to fibronectin by recognition of a specific peptide sequence, Arg-Gly-Asp-Ser (RGDS), in the fibronectin molecule (Pierschbacher and Ruoslahti, Proc Natl Acad Sci USA 81:5985-5988, 1984). We have used antibodies to integrin and an RGDS synthetic peptide to probe the functions of integrin in the migration of growth cones extended from sensory and spinal cord neurons of chick embryos. Analyses of time lapse videotapes of growth cone migration before and after adding RGDS indicated that 2 mM RGDS rapidly inhibits growth cone movement on substrata coated with fibronectin or a fragment of fibronectin containing the RGDS sequence. RGDS has no effect on growth cone movement on laminin or on a surface coated with material deposited from heart conditioned medium. However, a monclonal antibody to the integrin complex (10 micrograms/ml CSAT) completely blocks growth cone movement on substrata treated with fibronectin, laminin, or heart conditioned medium. Thus integrin may be involved in growth cone adhesion to several extracellular molecules, although the selective effects of RGDS indicate that the integrin complex may have heterogeneous sites for interaction with different components of the extracellular matrix. CSAT antibody has no discernible effect, however, on growth cone migration across the upper surfaces of C6 glioma cells. These data indicate that the surfaces of nerve growth cones contain multiple binding molecules that mediate different adhesive interactions during migration.