Diglons are heterodimeric proteins composed of IgLON subunits, and Diglon-CO inhibits neurite outgrowth from cerebellar granule cells.

IgLONs are a family of four cell adhesion molecules belonging to the Ig superfamily that are thought to play a role in cell-cell recognition and growth-cone migration. One member of the family, opioid-binding cell-adhesion molecule (OBCAM), might act as a tumour suppressor. Previous work has shown that limbic-system-associated protein (LAMP), CEPU-1/Neurotrimin and OBCAM interact homophilically and heterophilically within the family. Here, we show that, based on their relative affinities, CEPU-1 might be both a homo- and a heterophilic cell adhesion molecule, whereas LAMP and OBCAM act only as heterophilic cell adhesion molecules. A binding assay using recombinant IgLONs fused to human Fc showed that IgLONs are organized in the plane of the membrane as heterodimers, and we propose that IgLONs function predominantly as subunits of heterodimeric proteins (Diglons). Thus, the four IgLONs can form six Diglons. Furthermore, although singly transfected cell lines have little effect on neurite outgrowth, CHO cell lines expressing both CEPU-1 and OBCAM (Diglon-CO) inhibit neurite outgrowth from cerebellar granule cells.