The neural cell recognition molecule neurofascin interacts with syntenin-1but not with syntenin-2, both of which reveal self-associating activity

Neurofascin belongs to the L1 subgroup of the immunoglobulin superfamily of cell adhesion molecules and is implicated in axonal growth and fasciculati on, We used yeast two-hybrid screening to identify proteins that interact w ith neurofascin intracellularly and therefore might link it to trafficking, spatial targeting, or signaling pathways, Here, we demonstrate that rat sy ntenin-1, previously published as syntenin, mda-9, or TACIP18 in human, is a neurofascin-binding protein that exhibits a wide-spread tissue expression pattern with a relative maximum in brain. Syntenin-1 was found not to inte ract with other vertebrate members of the L1 subgroup such as L1 itself or NrCAM, We confirmed the specificity of the neurofascin-syntenin-1 interacti on by ligand-overlay assay, surface plasmon resonance analysis, and colocal ization of both proteins in heterologous cells. The COOH terminus of neurof ascin was mapped to interact with the second PDZ domain of syntenin-1. Furt hermore, we isolated syntenin-2 that may be expressed in two isoforms, Desp ite their high sequence similarity to syntenin-1, syntenin-2 alpha, which i nteracts with neurexin I, and syntenin-2 beta do not bind to neurofascin or several other transmembrane proteins that are binding partners of syntenin -1, Finally, we report that syntenin-1 and -2 both form homodimers and can interact with each other.