A FUNCTIONAL INTERACTION BETWEEN THE NEURONAL ADHESION MOLECULES TAG-1 AND F3 MODULATES NEURITE OUTGROWTH AND FASCICULATION OF CEREBELLAR GRANULE CELLS

F3 and TAG-1 are two closely related adhesion glycoproteins of the Ig superfamily that are both expressed by the axons of cerebellar granule cells. In an in vitro system in which cerebellar granule cells were c ultured on monolayers of transfected Chinese hamster ovary (CHO) cells , we show that F3 and TAG-1 interact functionally. F3 transfectants ha ve been shown to in hibit outgrowth and induce fasciculation of granul e cell neurites. By contrast TAG-1 transfectants have no effect on the se events. However, when TAG-1 is coexpressed with F3, the inhibitory effect of F3 is blocked. Two possible mechanisms may account for this functional interaction: (1) either TAG-1 and F3 compete for the same n euronal receptor, and in favor of this we observed that binding sites for microspheres conjugated with F3 and TAG-1 are colocalized on the g ranule cell growth cones, (2) or alternatively, F3 and TAG-1 associate in a multimolecular complex after their binding to independent recept ors. Extensive co-clustering of F3 with TAG-1 can in fact be achieved by anti-TAG-1 antibody-mediated cross-linking in double-transfected CH O cells. Moreover, F3 coimmunoprecipitates with TAG-1 in Triton X-100- insoluble microdomains purified from newborn brain. These data strongl y suggest that F3 and TAG-1 may associate under physiological conditio ns to modulate neurite outgrowth and fasciculation of the cerebellar g ranule cells.