DISTINCT EFFECTS OF RECOMBINANT TENASCIN-R DOMAINS IN NEURONAL CELL FUNCTIONS AND IDENTIFICATION OF THE DOMAIN INTERACTING WITH THE NEURONAL RECOGNITION MOLECULE F3 11/

We have identified distinct domains of the rat extracellular matrix gl ycoprotein tenascin-R using recombinant fragments of the molecule that confer neuronal cell functions. In short-term adhesion assays (0.5 h) , cerebellar neurons adhered best to the fragment representing the fib rinogen knob (FG), but also the fibronectin type III (FN) repeats 1-2 and 6-8. FG, FN1-2 and FN3-5 were the most repellent fragments for neu ronal cell bodies. Neurites and growth cones were strongly repelled fr om areas coated with fragments containing the cysteine-rich stretch an d the EGF-like domains (EGF-L), FN1-2, FN3-5 and FG, Polarization of m orphology of hippocampal neurons was exclusively associated with FG, w hile EGF-L prevented neurite outgrowth altogether. The binding site of the neuronal receptor for tenascin-R, the immunoglobulin superfamily adhesion molecule F3/11, was localized to EGF-L. The combined observat ions show distinct, but also overlapping functions for the different t enascin-R domains. They further suggest the existence of multiple neur onal tenascin-R receptors which influence the response of neurons to t heir extracellular matrix environment.