The role of human natural killer-1 (HNK-1) carbohydrate in neuronal plasticity and disease

• Published in: Biochimica et biophysica acta. General subjects 2017-10, Vol.1861 (10), p.2455-2461
• Main Authors: Morise, Jyoji, Takematsu, Hiromu, Oka, Shogo
• Format: Article
• Language: English
• Subjects: Aggrecans - metabolism; AMPA receptor; Animals; Anti-MAG neuropathy; Autoantibodies - biosynthesis; CD57 Antigens - chemistry; CD57 Antigens - genetics; CD57 Antigens - immunology; Epitopes - chemistry; Epitopes - genetics; Epitopes - immunology; Glucuronosyltransferase - deficiency; Glucuronosyltransferase - genetics; Glucuronyltransferase; HNK-1epitope; Humans; Immunoglobulin M - biosynthesis; Killer Cells, Natural - immunology; Killer Cells, Natural - pathology; Mice; Mice, Knockout; Myelin-Associated Glycoprotein - genetics; Myelin-Associated Glycoprotein - immunology; Neuronal Plasticity; Paraproteinemias - genetics; Paraproteinemias - immunology; Paraproteinemias - pathology; Perineuronal nets; Peripheral Nervous System Diseases - genetics; Peripheral Nervous System Diseases - immunology; Peripheral Nervous System Diseases - pathology; Receptors, AMPA - genetics; Receptors, AMPA - immunology; Synaptic plasticity
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2017.06.025

The human natural killer-1 (HNK-1) carbohydrate, a unique trisaccharide possessing sulfated glucuronic acid in a non-reducing terminus (HSO3-3GlcAß1-3Galß1-4GlcNAc-), is highly expressed in the nervous system and its spatiotemporal expression is strictly regulated. Mice deficient in the gene encoding a key enzyme, GlcAT-P, of the HNK-1 biosynthetic pathway exhibit almost complete disappearance of the HNK-1 epitope in the brain, significant reduction of long-term potentiation, and aberration of spatial learning and memory formation. In addition to its physiological roles in higher brain function, the HNK-1 carbohydrate has attracted considerable attention as an autoantigen associated with peripheral demyelinative neuropathy, which relates to IgM paraproteinemia, because of high immunogenicity. It has been suggested, however, that serum autoantibodies in IgM anti-myelin-associated glycoprotein (MAG) antibody-associated neuropathy patients show heterogeneous reactivity to the HNK-1 epitope. We have found that structurally distinct HNK-1 epitopes are expressed in specific proteins in the nervous system. Here, we overview the current knowledge of the involvement of these HNK-1 epitopes in the regulation of neural plasticity and discuss the impact of different HNK-1 antigens of anti-MAG neuropathy patients. We identified the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor subunit GluA2 and aggrecan as HNK-1 carrier proteins. The HNK-1 epitope on GluA2 and aggrecan regulates neural plasticity in different ways. Furthermore, we found the clinical relationship between reactivity of autoantibodies to the different HNK-1 epitopes and progression of anti-MAG neuropathy. The HNK-1 epitope is indispensable for the acquisition of normal neuronal function and can be a good target for the establishment of diagnostic criteria for anti-MAG neuropathy. •HNK-1 epitope is a unique trisaccharide expressed in the nervous system.•HNK-1 epitope on AMPA-type glutamate receptor regulates synaptic plasticity.•A novel HNK-1 epitope on aggrecan is specifically expressed in perineuronal nets.•HNK-1 epitope is related to neuronal diseases such as anti-MAG neuropathy.