Functional Regulation of Cell Adhesion Molecules by Neural Specific Carbohydrate

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The HNK-1 carbohydrate is characteristically expressed on a series of cell adhesion molecules and also on some glycolipids in the nervous system. The HNK-1 carbohydrate thought to be involved in cellcell and/or cellsubstrate interaction and recognition during the development of the nervous system. The characteristic structural feature of this carbohydrate is the sulfoglucuronyl residue, because the inner structure, Gal β1-4 GlcNAc, is found commonly in various glycoproteins and glycolipids. We cloned novel glucuronyltransferases (GlcAT-P and GlcAT-S), which are key enzymes involved in the biosynthesis of this carbohydrate. We have recently generated mice with a targeted deletion of the GlcAT-P gene. In the present study, we obtained following results using the GlcAT-P deficient mice. 1) The GlcAT-P deficient mice exhibited normal development of gross anatomical features but the adult mutant mice exhibited reduced longterm potentiation (LTP) at the Schaffer colIateral-CA1 synapses and defect in spatial memory formation. 2) In GlcAT-P deficient mice, the HNK-1 carbohydrate disappeared almost completely but a trace of HNK-1 immunoreactivity remained on the surfaces of soma and proximal dendrites of a subset of neurons in some limited regions. The remaining HNK-1 carbohydrate in the GlcAT-P deficient mice is synthesized by enzyme(s) other than GlcAT-P, presumably GlcAT-S