Overlapping and differential expression of BIG-2, BIG-1, TAG-1, and F3: four members of an axon-associated cell adhesion molecule subgroup of the immunoglobulin superfamily.

Axon-associated cell adhesion molecules (AxCAMs) play crucial roles in the formation, maintenance, and plasticity of functional neuronal networks. We report here a molecular cloning of a novel AxCAM, BIG-2. BIG-2 is a member of TAG-1/F3 subgroup of the immunoglobulin (Ig) superfamily, with six Ig-like domains, four fibronectin type III-like repeats, and a glycosyl phosphatidylinositol-anchoring domain. Recombinant BIG-2 protein had a neurite outgrowth-promoting activity when used as a substrate for neurons in vitro. To survey the spatial expression pattern of BIG-2 in comparison with other TAG-1/F3 subgroup members, an in situ hybridization analysis was performed in adult and developing rat brain sections with riboprobes specific for BIG-2, BIG-1, TAG-1, and F3. The four AxCAM transcripts displayed cell type-specific expression patterns with overlapping and distinct profiles. In adult hippocampus, for example, we observed BIG-1 mRNA specifically in granule cells of the dentate gyrus, BIG-2 mRNA highly in the CA1 pyramidal cells, TAG-1 mRNA predominantly in the CA3 pyramidal cells, and F3 mRNA in neurons in all of these fields. These results suggest that BIG-2, BIG-1, TAG-1, and F3 may play important roles in the formation and maintenance of specific neuronal networks in the brain.