Roles of the HNK-1 carbohydrate epitope in the nervous system

The HNK- epitope, 3-sulfo-glucuronyl residue is expressed specifically on a series of cell adhesion molecules and on some glycolipids in the nervous system over a wide range of species, and its expression is spatially and temporally regulated during the development of the nervous system. To study the biological functions of the epitope, we have cloned the enzymes that are involved in the biosynthesis of the epitope, glucuronyltransferse (GlcAT-P and GlcAT-S) and sulfotransferase (Sulf-T), A Northern blot analysis of GlcAT mRNAs in various rat tissues indicated that GlcAT-P and -S are the brain-specific or neural-specific enzymes. Upon transfection of the full length GlcAT-P cDNA into COS-1 cells, which do not express the HNK-lepitope, cells were transformed into HNK-1 positive cells. These cells showed dramatic changes of the cell architecture. They had long and branched processes with irregular shapes and several micro spikes on the soma and processes. Another function of the HNK-1 epitope is the inhibition of cell-cell aggregation. Thus control COS-1 cells formed huge aggregates after incubation at room temperature for 90 min, and most of the HNK-1 positive cells remained as free single cells.