Co-localisation, heterophilic interactions and regulated expression of IgLON family proteins in the chick nervous system

The chick glycoprotein GP55 has been shown to inhibit the growth and adhesi on of DRG and forebrain neurons. GP55 consists of several members of the Ig LON family, a group of glycoproteins including LAMP, OBCAM, CEPU-1 (chick)/ neurotrimin (rat) and neurotractin (chick)/kilon (rat) thought to play a ro le in the guidance of growing axons. IgLONs belong to the Ig superfamily an d have three C2 domains and a glycosyl phosphatidylinositol anchor which te thers them to the neuronal plasma membrane. We have now completed the deduc ed amino acid sequence for two isoforms of chicken OBCAM and used recombina nt LAMP, OBCAM and CEPU-1 to raise antisera specific to these three IgLONs. LAMP and CEPU-1 are co-expressed on DRG and sympathetic neurons, while bot h overlapping and distinct expression patterns for LAMP, OBCAM and CEPU-1 a re observed in retina. Analysis of IgLON mRNA expression reveals that alter natively spliced forms of LAMP and CEPU-1 are developmentally regulated. In an attempt to understand how the IgLONs function, we have begun to charact erise their molecular interactions. LAMP and CEPU-1 have already been shown to interact homophilically. We now confirm that OBCAM will bind homophilic ally and also that LAMP, OBCAM and CEPU-1 will interact heterophilically wi th each other. We propose that IgLON activity will depend on the complement of IgLONs expressed by each neuron. (C) 2000 Elsevier Science B.V. All rig hts reserved.