Disease relevance of B3gat1

• These unusual lipids have been reported as antigenic determinants for monoclonal IgM antibodies produced in patients with neuropathy associated with paraproteinemia and react with the mouse monoclonal antibody HNK-1 [1].
• Regulation of expression of sulfoglucuronyl carbohydrate (HNK-1), Amphoterin and RAGE in retinoic acid-differentiated P19 embryonal carcinoma cells [2].
• The mouse monoclonal antibody HNK-1 and the human monoclonal IgM antibody present in patients with polyneuropathy both recognize carbohydrate epitope(s) on human myelin-associated glycoprotein and P0 [3].
• Both populations of GFA protein and vimentin-positive astrocytes express N-CAM and the L2/HNK-1 epitope, but not tetanus toxin receptors or A2B5 antigen, at levels detectable by indirect immunofluorescence procedures [4].

High impact information on B3gat1

• The J1 glycoprotein--a novel nervous system cell adhesion molecule of the L2/HNK-1 family [5].
• To test this hypothesis, we have prepared polyclonal antibodies to a prominent member of the L2/HNK-1 family, the 160K (relative molecular mass (Mr)160,000) glycoprotein [5].
• Neural cell adhesion molecules and myelin-associated glycoprotein share a common carbohydrate moiety recognized by monoclonal antibodies L2 and HNK-1 [6].
• We show here that a mouse monoclonal antibody, HNK-1, which is directed against human natural killer cells also recognizes an antigenic determinant of human central and peripheral nervous system white matter by immunoperoxidase staining of tissue sections [7].
• We have recently characterized a chondroitin sulfate proteoglycan from the murine central nervous system which is expressed by astrocytes in vitro and carries the L2/HNK-1 and L5 carbohydrate structures [8].

Biological context of B3gat1

• The HNK-1 glycan, sulfo-->3GlcAbeta1-->3Galbeta1-->4GlcNAcbeta1-->R, is highly expressed in neuronal cells and apparently plays critical roles in neuronal cell migration and axonal extension [9].
• The L2/HNK-1 carbohydrate of neural cell adhesion molecules is involved in cell interactions [10].
• The GlcAT-P -/- mice exhibited normal development of gross anatomical features, but the adult mutant mice exhibited reduced long term potentiation at the Schaffer collateral-CA1 synapses and a defect in spatial memory formation [11].
• The Golgi-resident enzyme glucuronyltransferase (GlcAT-P) was a carbonylated target that we investigated further owing to its involvement in the biosynthesis of HNK-1, a carbohydrate epitope expressed on cell adhesion molecules and implicated in modulating the effectiveness of synaptic transmission in the brain [12].
• Reduced neuronal expression of synaptic transmission modulator HNK-1/neural cell adhesion molecule as a potential consequence of amyloid beta-mediated oxidative stress: a proteomic approach [12].

Anatomical context of B3gat1

• These results are consistent with our results showing that HNK-1 glycan is minimally attached to O-glycans of NCAM in fetal brain, heart, and the myoblast cell line, C2C12 [9].
• Specific expression of an HNK-1 carbohydrate epitope and NCAM on femoral nerve Schwann cells in mice [13].
• We used immunohistological analysis of femoral nerve segments containing sensory and motor fascicles, stained with anti-HNK-1, M6749 and anti-neural cell adhesion molecule (NCAM) monoclonal antibodies [13].
• Schwann cells from early postnatal mouse sciatic nerve were obtained as a homogenous population and shown by indirect immunofluorescence to express the neural cell adhesion molecules L1, N-CAM and J1 and their common carbohydrate epitope L2/HNK-1 [14].
• Immunofluorescence staining with antibody M6749 revealed that the non-sulfated HNK-1 carbohydrate was expressed predominantly on the apical membranes of the proximal tubules in the cortex and was also detected in the thin ascending limb in the inner medulla [15].

Associations of B3gat1 with chemical compounds

• The HNK-1 glycan synthesis is initiated by the addition of beta1,3-linked GlcA to N-acetyllactosamine followed by sulfation of the C-3 position of GlcA [9].
• The most straightforward interpretation of these observations is that the L2/HNK-1 carbohydrate and the sulfated carbohydrates, sulfatide and heparin, act as ligands in cell adhesion [10].
• These results suggested that the HNK-1 carbohydrate without sulfate (non-sulfated HNK-1 carbohydrate) is expressed in the kidney [15].
• The HNK-1 carbohydrate epitope, a sulfated glucuronic acid at the non-reducing terminus of glycans, is expressed characteristically on a series of cell adhesion molecules and is synthesized through a key enzyme, glucuronyltransferase (GlcAT-P) [11].
• The characteristic structural feature of the HNK-1 carbohydrate is 3-sulfo-glucuronyl residues attached to lactosamine structures (Gal beta1-4GlcNAc) on glycoproteins and glycolipids [15].

Other interactions of B3gat1

• By contrast, HNK-1 glycan was much more efficiently added to N-glycans than O-glycans when NCAM was used as an acceptor [9].
• Using synthetic oligosaccharides as acceptors, we found that GlcAT-P and HNK-1ST almost equally act on oligosaccharides, mimicking N- and O-glycans [9].
• This is the first study indicating the presence of the non-sulfated HNK-1 carbohydrate being synthesized by GlcAT-S in the kidney [15].
• These results provide first evidence that tenascin-R and its associated HNK-1 carbohydrate modulate perisomatic inhibition and synaptic plasticity in the hippocampus [16].
• This protein is post-translationally modified with oligosaccharides, including the HNK-1 epitope, but, unlike phosphacan, it is not a proteoglycan [17].

Analytical, diagnostic and therapeutic context of B3gat1

• Since indirect evidence indicated that the L2/HNK-1 carbohydrate is not present on all molecules within a particular species of glycoproteins, it seemed pertinent to investigate this more directly by sequential immunoprecipitations [18].
• Molecular cloning and genomic analysis of mouse glucuronyltransferase involved in biosynthesis of the HNK-1 epitope [19].
• HNK-1 immunohistochemistry revealed that clusters of HNK-1-positive cells (presumptive migrating neural crest cells) are frequently located around the developing eyes and in the posterior region of the silver embryonic eye [20].
• These findings reveal alterations in ST-/- mice that differ from EEG abnormalities of mice deficient in the HNK-1 carrier molecule tenascin-R [21].
• Western blot analyses of the neural cell adhesion molecules (N-CAMs) during development of the rat cortex with a polyclonal anti-N-CAM antibody showed that the major HNK-1-reactive protein bands were not N-CAMs [22].

References