From the discovery of neuropilin to the determination of its adhesion sites.

Neuropilin (NRP) and plexin (Plex) that are now known to be semaphorin receptors were initially identified as antigens for monoclonal antibodies (MAbs) that bound to particular neuropiles and plexiform layers of the Xenopus tadpole optic tectum, several years before the discovery of semaphorin. The extracellular segment of the NRP protein is a mosaic of 3 functionally different protein motifs that are thought to be involved in molecular and/or cellular interactions, suggesting that NRP serves in a various cell-cell interaction by binding a variety of molecules. The first identified function of NRP was the cell adhesion activity; Cell reaggregation study using NRP-expressing cell lines revealed that NRP can mediate cell adhesion via heterophilic molecular interaction. Later, NRP was shown to bind semaphorins and vascular endothelial growth factor (VEGF). It was also shown that NRP makes receptor complexes with Plex to propagate semaphorin signals.