Biological functions of the neural specific carbohydrate antigen, hnk-1

The HNK-1 carbohydrate epitope is expressed in a stage specific manner on a series of neural cell adhesion molecules such as NCAM, PO as well as on some glycolipids in the nervous system over a wide range of species from insect to mammals. The structure of the HNK-1 epitope is revealed as a sulfated trisaccharide S04-3GIcAbetal-3Galbetal-4GlcNAc, which is shared with glycolipid and glycoprotein antigens. Recently, we cloned a glucuronyltransferase (GlcAT-P) cDNA from a rat brain cDNA library, which is associated with the biosynthesis of the HNK-1 epitope on glycoproteins (1). The mature protein is composed of 347 ainino acid residues of a predicted molecular weight of 39,706 with 3 potential N-glycosylation sites. Northern blot analysis indicated that the glucuronyltransferase gene was expressed almost exclusively in the brain, being consistent with the specific localization of the HNK-1 epitope in the nervous system. In situ hybridization analysis indicated a characteristic distribution of the enzyme mRNA in various regions of rat brain. Transfection of the glucuronyltransferase cDNA into COS-1 cells and C6 glioma cells induced not only expression of the HNK-1 epitope on the cell surface but also marked morphological changes of the cells and profound inhibitory effects on the homophilic cell-cell aggregation, suggesting that the HNK-1 epitope itself has an ability to modulate the cell-substratum interaction and cell to cell adhesion. 1) Terayama, K.. H al.. Proc. Natl. Acad. Sri, USA, 94 6093-6098 (1997).