AXONAL GLYCOPROTEINS WITH IMMUNOGLOBULIN AND FIBRONECTIN TYPE-III-RELATED DOMAINS IN VERTEBRATES - STRUCTURAL FEATURES, BINDING ACTIVITIES, AND SIGNAL-TRANSDUCTION

The L1- and F11-like axonal glycoproteins, implicated in neurite outgrowth and fasciculation, are members of the Ig superfamily comprising multiple fibronectin type III-like domains. Their Ig-like and fibronectin type III-related domains are likely to be composed of seven beta-strands arranged in two opposing beta-sheets of highly similar topology. Whereas the F11-like molecules lack a transmembrane sequence and are anchored in the plasma membrane by a glycosylphosphatidylinositol, the L1-like molecules comprise cytoplasmic domains with highly conserved sequence motifs. Most of the latter proteins occur in different isoforms generated by alternative pre-mRNA splicing, which has not been documented for molecules of the F11 subgroup. L1-like proteins undergo heterophilic as well as homophilic interactions, whereas only the former mode of binding was observed for F11-like proteins. Evidence is accumulating that these Ig superfamily molecules with fibronectin type III-like domains are interacting in a complex manner with each other and molecules of the extracellular matrix. Investigations assigning structure to function reveal that their individual extracellular domains serve distinct binding activities. Recent studies also suggest that L1 and NCAM are implicated in the transduction of transmembrane signals.