Jyoji Morise1, Hiromu Takematsu1, Shogo Oka2. 1. Department of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. 2. Department of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan. Electronic address: shogo@hs.med.kyoto-u.ac.jp.
Abstract
BACKGROUND: 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. SCOPE OF REVIEW: 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. MAJOR CONCLUSIONS: 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. GENERAL SIGNIFICANCE: 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.
BACKGROUND: 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-1carbohydrate 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 neuropathypatients show heterogeneous reactivity to the HNK-1 epitope. SCOPE OF REVIEW: 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 neuropathypatients. MAJOR CONCLUSIONS: 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. GENERAL SIGNIFICANCE: 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.
Authors: M Osman Sheikh; David Venzke; Mary E Anderson; Takako Yoshida-Moriguchi; John N Glushka; Alison V Nairn; Melina Galizzi; Kelley W Moremen; Kevin P Campbell; Lance Wells Journal: Glycobiology Date: 2020-09-28 Impact factor: 4.313
Authors: Martina Pigoni; Hung-En Hsia; Jana Hartmann; Jasenka Rudan Njavro; Merav D Shmueli; Stephan A Müller; Gökhan Güner; Johanna Tüshaus; Peer-Hendrik Kuhn; Rohit Kumar; Pan Gao; Mai Ly Tran; Bulat Ramazanov; Birgit Blank; Agnes L Hipgrave Ederveen; Julia Von Blume; Christophe Mulle; Jenny M Gunnersen; Manfred Wuhrer; Gerhard Rammes; Marc Aurel Busche; Thomas Koeglsperger; Stefan F Lichtenthaler Journal: EMBO J Date: 2020-06-22 Impact factor: 11.598