Expression and biological functions of sulfoglucuronyl glycolipids (SGGLs) in the nervous system—A review

Sulfoglucuronyl carbohydrate linked to neolactotetraose reacts with HNK-1 antibody. The HNK-1 carbohydrate epitope is found in two major glycolipids, several glycoproteins and in some proteoglycans of the nervous system. Most of the HNK-1 reactive glycoproteins so far identified are neural cell adhesion molecules and/or are involved in cell-cell interactions. HNK-1 carbohydrate is highly immunogenic. Several HNK-1-like antibodies, including IgM of some patients with plasma cell abnormalities and having peripheral neuropathy, have been described. This article summarizes published work mainly on sulfoglucuronyl glycolipids, SGGLs and covers: structural requirements of the carbohydrate epitope for binding to HNK-1 and human antibodies, expression of the lipids in various neural areas, stage and region specific developmental expression in CNS and PNS, immunocytochemical localization, loss of expression in Purkinje cell abnormality murine mutations, biosynthetic regulation of expression by a single enzyme N-acetylglucosaminyl transferase, identification of receptor-like carbohydrate binding neural proteins (lectins), and perceived role of the carbohydrate in physiological functions. The latter includes role in: pathogenesis of certain peripheral neuropathies, in migration of neural crest cells, as a ligand in cell-cell adhesion/interaction and as a promoter of neurite outgrowth for motor neurons. Multiple expression of HNK-1 carbohydrate in several molecules and in various neural cell types at specific stages of nervous system development has puzzled investigators as to its specific biological function, but this may also suggest its importance in multiple systems during cell differentiation and migration processes.

[1]  R. Kalb,et al.  Induction of demyelination by intraneural injection of antibodies against sulfoglucuronyl paragloboside , 1991, Experimental Neurology.

[2]  A. Steck,et al.  Human myelin/oligodendrocyte glycoprotein: a new member of the L2/HNK-1 family. , 1993, Journal of neurochemistry.

[3]  T. Kohriyama,et al.  Sulfated Glucuronyl Paragloboside in Rat Brain Microvessels , 1990, Journal of neurochemistry.

[4]  Arne Møller,et al.  Total numbers of various cell types in rat cerebellar cortex estimated using an unbiased stereological method , 1993, Brain Research.

[5]  M. Schachner Families of neural adhesion molecules. , 1989, Ciba Foundation symposium.

[6]  F. Jungalwala,et al.  Characterization and developmental expression of a novel sulfotransferase for the biosynthesis of sulfoglucuronyl glycolipids in the nervous system. , 1993, The Journal of biological chemistry.

[7]  M. Watson,et al.  Cloning and expression of a developmentally regulated protein that induces mitogenic and neurite outgrowth activity. , 1990, Science.

[8]  C. Brosnan,et al.  Preliminary studies on sensitization of Lewis rats with sulfated glucuronyl paragloboside , 1991, Brain Research.

[9]  V. Caviness,et al.  Distribution of glucuronic acid-and-sulfate-containing glycoproteins in the central nervous system of the adult mouse , 1988, Neurosciences research.

[10]  N. Prasadarao,et al.  Developmental Expression of HNK‐1‐Reactive Antigens in the Rat Cerebellum and Localization of Sulfoglucuronyl Glycolipids in Molecular Layer and Deep Cerebellar Nuclei , 1990, Journal of neurochemistry.

[11]  J. Altman,et al.  Embryonic development of the rat cerebellum. I. Delineation of the cerebellar primordium and early cell movements , 1985, The Journal of comparative neurology.

[12]  R. Yu,et al.  Localization of glycoconjugates recognized by the HNK-1 antibody in mouse and chick embryos during early neural development. , 1987, Developmental neuroscience.

[13]  H. Rauvala,et al.  Amphoterin, the 30-kDa protein in a family of HMG1-type polypeptides. Enhanced expression in transformed cells, leading edge localization, and interactions with plasminogen activation. , 1993, The Journal of biological chemistry.

[14]  P S Mohan,et al.  Sulfoglucuronyl Glycolipids Bind Laminin , 1990, Journal of neurochemistry.

[15]  E. Shooter,et al.  Rapid Communication: Human Peripheral Myelin Protein‐22 Carries the L2/HNK‐1 Carbohydrate Adhesion Epitope , 1993, Journal of neurochemistry.

[16]  R. Matsas,et al.  Monoclonal antibody BM89 recognizes a novel cell surface glycoprotein of the L2/HNK-1 family in the developing mammalian nervous system , 1992, Neuroscience.

[17]  N. Prasadarao,et al.  Developmental Expression of HNK‐1‐Reactive Antigens in Rat Cerebral Cortex and Molecular Heterogeneity of Sulfoglucuronylneolactotetraosylceramide in CNS Versus PNS , 1991, Journal of neurochemistry.

[18]  M. Daston,et al.  Expression of P30, a protein with adhesive properties, in Schwann cells and neurons of the developing and regenerating peripheral nerve , 1991, The Journal of cell biology.

[19]  J. Wu,et al.  Glutamate decarboxylase‐immunoreactive structures in the rat neostriatum: A correlated light and electron microscopic study including a combination of Golgi impregnation with immunocytochemistry , 1985, The Journal of comparative neurology.

[20]  A. Hays,et al.  Experimental demyelination of nerve induced by serum of patients with neuropathy and an anti‐MAG IgM M‐protein , 1987, Neurology.

[21]  K. Das,et al.  Biosynthesis in vitro of GlcA beta 1-3nLcOse4Cer by a novel glucuronyltransferase (GlcAT-1) from embryonic chicken brain. , 1991, The Journal of biological chemistry.

[22]  H. Lassmann,et al.  A shared antigenic determinant between natural killer cells and nervous tissue , 1983, Nature.

[23]  R. Schnaar,et al.  The HNK-1 reactive sulfoglucuronyl glycolipids are ligands for L-selectin and P-selectin but not E-selectin. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[24]  S. Kusunoki,et al.  Subcellular Localization of Sulfated Glucuronic Acid‐Containing Glycolipids Reacting with Anti‐Myelin‐Associated Glycoprotein Antibody , 1987, Journal of neurochemistry.

[25]  S. Bon,et al.  Expression and localization in the developing cerebellum of the carbohydrate epitopes revealed by Elec-39, an IGM monoclonal antibody related to HNK-1 , 1991, Neuroscience.

[26]  F. Jungalwala,et al.  Sulfoglucuronyl Neolactoglycolipids in Adult Cerebellum: Specific Absence in Murine Mutants with Purkinje Cell Abnormality , 1988, Journal of neurochemistry.

[27]  H. Rauvala,et al.  Sulfoglycolipids bind to adhesive protein amphoterin (P30) in the nervous system. , 1992, Biochemical and biophysical research communications.

[28]  J. Evans,et al.  Sulfoglucuronyl‐Neolacto Series of Glycolipids in Peripheral Nerves Reacting with HNK‐1 Antibody , 1987, Journal of neurochemistry.

[29]  E. Bock,et al.  Glycosylation of neural cell adhesion molecules of the immunoglobulin superfamily. , 1992, APMIS. Supplementum.

[30]  A. Hennig,et al.  Two immunologically and developmentally distinct chondroitin sulfate proteolglycans in embryonic chick brain. , 1992, The Journal of biological chemistry.

[31]  S. Oka,et al.  A novel glucuronyltransferase in nervous system presumably associated with the biosynthesis of HNK-1 carbohydrate epitope on glycoproteins. , 1992, The Journal of biological chemistry.

[32]  B. Trapp,et al.  IgM in a human neuropathy related to paraproteinemia binds to a carbohydrate determinant in the myelin-associated glycoprotein and to a ganglioside. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[33]  C. Costello,et al.  Variability in the Structural Requirements for Binding of Human Monoclonal Anti‐Myelin‐Associated Glycoprotein Immunoglobulin M Antibodies and HNK‐1 to Sphingoglycolipid Antigens , 1990, Journal of neurochemistry.

[34]  G. Schwarting,et al.  Sulfated glucuronic acid-containing glycoconjugates are temporally and spatially regulated antigens in the developing mammalian nervous system. , 1987, Developmental biology.

[35]  F. Jungalwala,et al.  Loss of Sulfoglucuronyl and Other Neolactoglycolipids in Purkinje Cell Abnormality Murine Mutants , 1990, Journal of neurochemistry.

[36]  F. Jungalwala,et al.  Characterization and Developmental Expression of Lactotriosylceramider: Galactosyltransferase for the Synthesis of Neolactotetraosylceramide in the Nervous System , 1994, Journal of neurochemistry.

[37]  L. Presta,et al.  P- and E-selectin use common sites for carbohydrate ligand recognition and cell adhesion , 1993, The Journal of cell biology.

[38]  M. Schachner,et al.  Expression of the neural cell adhesion molecules L1 and N-CAM and their common carbohydrate epitope L2/HNK-1 during development and after transection of the mouse sciatic nerve. , 1985, Differentiation; research in biological diversity.

[39]  M. Schachner,et al.  Immunocytological localization of the major peripheral nervous system glycoprotein P0 and the L2/HNK-1 and L3 carbohydrate structures in developing and adult mouse sciatic nerve. , 1988, Developmental biology.

[40]  M. Schachner,et al.  Neural cell adhesion molecules and myelin-associated glycoprotein share a common carbohydrate moiety recognized by monoclonal antibodies L2 and HNK-1 , 1984, Nature.

[41]  M. Schachner,et al.  Cell type specificity and developmental expression of the L2/HNK-1 epitopes in mouse cerebellum , 1985, Journal of Neuroimmunology.

[42]  Y. Ito,et al.  Synthesis of sulfated glucuronyl glycosphingolipids; carbohydrate epitopes of neural cell-adhesion molecules. , 1993, Carbohydrate research.

[43]  F. Jungalwala,et al.  Expression and regulation of UDP-glucuronate: neolactotetraosylceramide glucuronyltransferase in the nervous system. , 1991, The Journal of biological chemistry.

[44]  M. Bronner‐Fraser Analysis of the early stages of trunk neural crest migration in avian embryos using monoclonal antibody HNK-1. , 1986, Developmental biology.

[45]  O. Breidbach,et al.  Insect glial cells show differential expression of a glycolipid-derived, glucuronic acid-containing epitope throughout neurogenesis: detection during postembryogenesis and regeneration in the central nervous system of Tenebrio molitor L. , 1992, Neuroscience Letters.

[46]  M. Schachner,et al.  Detection of the L2/HNK‐1 Carbohydrate Epitope on Glycoproteins and Acidic Glycolipids of the Insect Calliphora vicina , 1988, Journal of neurochemistry.

[47]  D. Newgreen,et al.  The migration of neural crest cells. , 1986, International review of cytology.

[48]  J. Fawcett,et al.  The migration of neural crest cells and the growth of motor axons through the rostral half of the chick somite. , 1985, Journal of embryology and experimental morphology.

[49]  A. Steck,et al.  Comparison of the N‐Linked Oligosaccharide Structures of the Two Major Human Myelin Glycoproteins MAG and P0: Assessment and Relative Occurrence of Oligosaccharide Structures by Serial Lectin Affinity Chromatography of 14C‐Glycopeptides , 1992, Journal of neurochemistry.

[50]  M. Schachner,et al.  Differential inhibition of neurone–neurone, neurone–astrocyte and astrocyte–astrocyte adhesion by L1, L2 and N-CAM antibodies , 1985, Nature.

[51]  N. Prasadarao,et al.  Rostrocaudal expression of antibody HNK‐1‐reactive glycolipids in mouse cerebellum: Relationship to developmental compartments and leaner mutation , 1993, The Journal of comparative neurology.

[52]  C. Balch,et al.  A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). , 1981, Journal of immunology.

[53]  M. Forbes,et al.  Spectrum of in vitro differentiation of quail trunk neural crest cells isolated by cell sorting using the HNK-1 antibody and analysis of the adrenergic development of HNK-1+ sorted subpopulations. , 1991, Journal of neurobiology.

[54]  J. Gulcher,et al.  The oligodendrocyte-myelin glycoprotein belongs to a distinct family of proteins and contains the HNK-1 carbohydrate , 1990, The Journal of cell biology.

[55]  L. Liotta,et al.  Comparison of the specificities of laminin, thrombospondin, and von Willebrand factor for binding to sulfated glycolipids. , 1986, The Journal of biological chemistry.

[56]  K. Das,et al.  Characterization of solubilized GlcAT-1 (UDP-GlcA: nLcOse4Cer beta 1-3 glucuronyltransferase) activity from embryonic chicken brain and its inhibition by D-erythro-sphingosine. , 1990, Indian journal of biochemistry & biophysics.

[57]  R. Schnaar,et al.  Carbohydrate recognition in the peripheral nervous system: a calcium- dependent membrane binding site for HNK-1 reactive glycolipids potentially involved in Schwann cell adhesion , 1993, The Journal of cell biology.

[58]  G. D. Maxwell,et al.  Temporal Expression of HNK‐1‐Reactive Sulfoglucuronyl Glycolipid in Cultured Quail Trunk Neural Crest Cells: Comparison with Other Developmentally Regulated Glycolipids , 1992, Journal of neurochemistry.

[59]  M. Schachner,et al.  The L2/HNK‐1 Carbohydrate Epitope is Involved in the Preferential Outgrowth of Motor Neurons on Ventral Roots and Motor Nerves , 1992, The European journal of neuroscience.

[60]  J. Guénet,et al.  Monoclonal antibody to neural cell surface protein: Identification of a glycoprotein family of restricted cellular localization , 1983, Neuroscience.

[61]  M. Schachner,et al.  The L2/HNK-1 carbohydrate of neural cell adhesion molecules is involved in cell interactions , 1988, The Journal of cell biology.

[62]  B. Pakkenberg,et al.  A quantitative study of the human cerebellum with unbiased stereological techniques , 1992, The Journal of comparative neurology.

[63]  N. Latov,et al.  Myelin‐Associated Glycoprotein Is the Antigen for a Monoclonal IgM in Polyneuropathy , 1982, Journal of neurochemistry.

[64]  J. Evans,et al.  Structure of a glycolipid reacting with monoclonal IgM in neuropathy and with HNK-1. , 1985, Biochemical and biophysical research communications.

[65]  N. Prasadarao,et al.  Effect of different fixatives on immunocytochemical localization of HNK-1-reactive antigens in cerebellum: a method for differentiating the localization of the same carbohydrate epitope on proteins vs lipids. , 1990, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[66]  H. Rauvala,et al.  30-kDa heparin-binding protein of brain (amphoterin) involved in neurite outgrowth. Amino acid sequence and localization in the filopodia of the advancing plasma membrane. , 1991, The Journal of biological chemistry.

[67]  P. Brophy,et al.  Protein zero of peripheral nerve myelin: Biosynthesis, membrane insertion, and evidence for homotypic interaction , 1990, Neuron.

[68]  J. Thiery,et al.  Identical reactivity of monoclonal antibodies HNK-1 and NC-1: conservation in vertebrates on cells derived from the neural primordium and on some leukocytes. , 1984, Cell differentiation.

[69]  J. Loring,et al.  Neural crest cell migratory pathways in the trunk of the chick embryo. , 1987, Developmental biology.

[70]  R. U. Margolis,et al.  Association of the HNK-1 epitope with 5'-nucleotidase from Torpedo marmorata (electric ray) electric organ. , 1991, The Biochemical journal.

[71]  H. Willison,et al.  Myelin‐Associated Glycoprotein and Related Glycoconjugates in Developing Cat Peripheral Nerve: A Correlative Biochemical and Morphometric Study , 1987, Journal of neurochemistry.

[72]  Mark C. Field,et al.  Detection of Multisulphated N‐Linked Glycans in the L2/HNK‐1 Carbohydrate Epitope Expressing Neural Adhesion Molecule P0 , 1992, Journal of neurochemistry.

[73]  V. Shashoua,et al.  Demonstration of glucuronic acid on brain glycoproteins which react with HNK-1 antibody. , 1986, Biochemical and biophysical research communications.

[74]  H. Rauvala,et al.  Molecular cloning of the 18-kDa growth-associated protein of developing brain. , 1990, The Journal of biological chemistry.

[75]  T. Kohriyama,et al.  Preparation and Characterization of Antibodies Against a Sulfated Glucuronic Acid‐Containing Glycosphingolipid , 1988, Journal of neurochemistry.

[76]  M. Hemling,et al.  Characterization of sulfated glucuronic acid containing glycolipids reacting with IgM M-proteins in patients with neuropathy. , 1987, The Journal of biological chemistry.

[77]  T. Jessell,et al.  Carbohydrates and carbohydrate-binding proteins in the nervous system. , 1990, Annual review of neuroscience.

[78]  S. Kusunoki,et al.  Localization of sulfated glucuronyl glycolipids in human dorsal root and sympathetic ganglia , 1990, Brain Research.

[79]  R. Heinrikson,et al.  SAG: a Schwann cell membrane glycoprotein , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[80]  J. Roder,et al.  Recognition of myelin-associated glycoprotein by the monoclonal antibody HNK-1 , 1983, Nature.

[81]  A. Steck,et al.  Human Myelin/Oligodendrocyte Glycoprotein: A New Member of the L2/HNK‐1 Family , 1993, Schweizer Archiv fur Neurologie und Psychiatrie.

[82]  A. Graham,et al.  The neural crest , 2003, Current Biology.

[83]  H. Rauvala An 18‐kd heparin‐binding protein of developing brain that is distinct from fibroblast growth factors. , 1989, The EMBO journal.

[84]  C. Barnstable,et al.  A carbohydrate epitope defined by monoclonal antibody VC1.1 is found on N-CAM and other cell adhesion molecules , 1991, Brain Research.

[85]  D. Tibboel,et al.  Characterization of HNK-1 antigens during the formation of the avian enteric nervous system. , 1992, Development.

[86]  H. Willison,et al.  Antibodies to glycolipids in demyelinating diseases of the human peripheral nervous system. , 1986, Chemistry and physics of lipids.

[87]  J. Evans,et al.  Structure of sulfated glucuronyl glycolipids in the nervous system reacting with HNK-1 antibody and some IgM paraproteins in neuropathy. , 1986, The Journal of biological chemistry.

[88]  H. Rauvala,et al.  Isolation and some characteristics of an adhesive factor of brain that enhances neurite outgrowth in central neurons. , 1987, The Journal of biological chemistry.

[89]  M. Schachner,et al.  L2/HNK‐1 carbohydrate and protein‐protein interactions mediate the homophilic binding of the neural adhesion molecule P0 , 1992, Journal of neuroscience research.

[90]  R. U. Margolis,et al.  Occurrence of the HNK-1 epitope (3-sulfoglucuronic acid) in PC12 pheochromocytoma cells, chromaffin granule membranes, and chondroitin sulfate proteoglycans. , 1987, Biochemical and biophysical research communications.

[91]  M. Bronner‐Fraser Perturbation of cranial neural crest migration by the HNK-1 antibody. , 1987, Developmental biology.