Functional interactions of the immunoglobulin superfamily member F11 are differentially regulated by the extracellular matrix proteins tenascin-R andtenascin-C

The axon-associated protein F11 is a GPI-anchored member of the immunoglobu lin superfamily that promotes axon outgrowth and that shows a complex bindi ng pattern toward multiple cell surface and extracellular matrix proteins i ncluding tenascin-R and tenascin-C. In this study, we demonstrate that tena scin-R and tenascin-C differentially modulate cell adhesion and neurite out growth of tectal cells on F11, While soluble tenascin-R increases the numbe r of attached cells and the percentage of cells with neurites on immobilize d F11, tenascin-C stimulates cell attachment to a similar extent but decrea ses neurite outgrowth. The cellular receptor interacting with F11 has been previously identified as NrCAM; however, in the presence of tenascin-a or t enascin-C cell attachment and neurite extension are independent of NrCAM. A ntibody perturbation experiments indicate that beta(1), integrins instead o f NrCAM function as receptor for neurite outgrowth of tectal cells on an F1 1 TN-R complex. Cellular binding assays support the possibility that the in teraction of F11 to NrCAM is blocked in the presence of tenascin-R and tena scin-C. Furthermore, a sandwich binding assay demonstrates that tenascin-R and tenascin-C are able to form larger molecular complexes and to link F11 polypeptides by forming a molecular bridge, These results suggest that the molecular interactions of F11 might be regul ated by the presence of tenascin-R and tenascin-C.