Bidirectional signaling between neurons and glial cells via the F3 neuronal adhesion molecule

F3, a glycosyl-phosphatidylinositol anchored molecule of the immunoglobulin superfamily, is known to influence axonal growth and fasciculation via multiple interactions of its modular immunoglobulin-like domains. We prepared a Fc chimeric molecule (F3IgFc) to identify a) the phenotype of cells bearing F3Ig receptors, b) the glial-expressed molecules interacting with these domains and, c) to characterize in in vitro models the functional impact of the interactions. We observed a strong binding of F3IgFc coated fluorospheres to astrocytes in neural primary cultures and to C6 astrocytoma cells. In agreement, in extracts of developing mouse brain F3IgFc is able to bind tenascin-R, tenascin-C, and isoforms of the proteoglycan-type protein tyrosine phosphatases z/beta. All these molecules are synthetized by glial cells as an indication that F3 participates in neuron-glia interactions. We showed that C6 glia-expressed PTPz/RPTP beta stimulated neurite outgrowth by cortical and cerebellar neurons whereas preclustered F3IgFc specifically modified the distribution and intensity of phosphotyrosine labeling in these glial cells. We also showed that inhibition of tenascin-R interaction with F3 prevented defasciculation of cerebellar explants which normally display a defasciculated outgrowth of neurites on a growth permissive substrate. These results identify F3, RTPz/RPTP beta, and tenascin-R as potential mediators of a reciprocal exchange of information between glia and neurons.