Developmental expression of receptor for advanced glycation end products (RAGE), amphoterin and sulfoglucuronyl (HNK-1) carbohydrate in mouse cerebellum and their role in neurite outgrowth and cell migration

Receptor for advanced glycation end products (RAGE) has been proposed as a signal transduction receptor to promote neurite outgrowth and cell migration, by its interaction with a neurite outgrowth promoting protein, Amphoterin. Amphoterin has been shown to interact with sulfoglucuronyl carbohydrate (SGC). The developmental expression of RAGE, Amphoterin and SGC was studied in pre-natal and post-natal mouse cerebellum to establish their cellular and subcellular localization and function. The amount of RAGE in the cerebellum increased with age. RAGE was expressed pre-natally in the external germinal layer and post-natally in the plasma membranes of the granule neurons of the external and internal granule cell layers and in Purkinje cells. Immunocytochemical analysis by high magnification confocal microscopy showed that RAGE was co-expressed with Amphoterin and SGC in the cell surfaces of granule neurons. This co-localization of RAGE, Amphoterin, and SGC was confirmed in isolated and cultured granule neurons and in migrating granule neurons in explant cultures. Anti-RAGE antibodies inhibited neurite outgrowth and cell migration in explant and slice cultures, similar to anti-Amphoterin and anti-SGC antibodies shown previously. The results suggest that RAGE could act as a signaling molecule for neurite outgrowth and cell migration by its interaction with Amphoterin and that of Amphoterin with SGC.