Receptor for advanced glycation end products (RAGE) mediates neuronal differentiation and neurite outgrowth.

The receptor for advanced glycation end products (RAGE) plays a crucial role in several disease processes, such as diabetes, inflammation, and neurodegeneration. In this article we report multiple roles of RAGE in neuronal differentiation and neurite outgrowth. In retinoic-induced P19 embryonic carcinoma stem cells, silencing the expression of RAGE by RNA interference (RNAi) blocked differentiation of the P19 cells into neuronal cells and enhanced the formation of vimentin-positive fibroblast-like cells.

Developmental expression of receptor for advanced glycation end products (RAGE), amphoterin and sulfoglucuronyl (HNK-1) carbohydrate in mouse cerebellum and their role in neurite outgrowth and cell migration.

Receptor for advanced glycation end products (RAGE) has been proposed as a signal transduction receptor to promote neurite outgrowth and cell migration, by its interaction with a neurite outgrowth promoting protein, Amphoterin. Amphoterin has been shown to interact with sulfoglucuronyl carbohydrate (SGC). The developmental expression of RAGE, Amphoterin and SGC was studied in pre-natal and post-natal mouse cerebellum to establish their cellular and subcellular localization and function.

Regulation of expression of sulfoglucuronyl carbohydrate (HNK-1), Amphoterin and RAGE in retinoic acid-differentiated P19 embryonal carcinoma cells.

HNK-1 antibody reactive sulfoglucuronyl carbohydrate (SGC) and SSEA-1 antibody reactive Lewis X (Lex) epitope are expressed on several glycolipids, glycoproteins, and proteoglycans of the nervous system and have been implicated in cell-cell recognition, neurite outgrowth, and/or neuronal migration during development. Interaction of SGC with its binding protein Amphoterin and interaction of Amphoterin with a cell-signaling molecule, receptor for advance glycation end product (RAGE) have been suggested to regulate neurite outgrowth and neuronal migration. The regulation of expression of SGC, Lex, Amphoterin, and RAGE was studied in embryonal carcinoma P19 cells after treatment with retinoic acid (RA).

HNK-1 sulfotransferase null mice express glucuronyl glycoconjugates and show normal cerebellar granule neuron migration in vivo and in vitro.

Sulfoglucuronyl carbohydrate (SGC), reactive with antibody against human natural killer cell antigen, is expressed in several glycolipids, glycoproteins and proteoglycans of the nervous system and has been implicated in cell-cell recognition, neurite outgrowth and neuronal migration during development, through its interaction with SGC-binding protein (SBP) 1. However, sulfotransferase (ST) null mutant mice, which lack SGC, were shown to have normal development with usual gross anatomy of the nervous system and other organs. Failure to observe a severe phenotype in the ST null mice prompted us to determine the compensatory molecular replacement of SGC by analyzing the carbohydrate of glycolipids and glycoproteins of the ST mutant nervous system.

Regulation of sulfoglucuronyl glycolipid synthesis in the developing rat sciatic nerve.

Sulfoglucuronyl glycolipids (SGGLs) have been considered as target antigens in demyelinating peripheral neuropathies associated with IgM monoclonal gammopathy. The regulation of expression of SGGLs in the rat sciatic nerve during development was studied by assaying the levels of SGGLs and activities of four glycosyltransferases sequentially involved in their synthesis from lactosylceramide. The levels of SGGLs in the sciatic nerve increased with development and reached a maximum at sixty days after birth.

Cloning of a mouse beta 1,3 N-acetylglucosaminyltransferase GlcNAc(beta 1,3)Gal(beta 1,4)Glc-ceramide synthase gene encoding the key regulator of lacto-series glycolipid biosynthesis.

The distinction between the different classes of glycolipids is conditioned by the action of specific core transferases. The entry point for lacto-series glycolipids is catalyzed by the beta1,3 N-acetylglucosaminyltransferase GlcNAc(beta1,3)Gal(beta1,4)Glc-ceramide (Lc3) synthase enzyme. The Lc3 synthase activity has been shown to be regulated during development, especially during brain morphogenesis.

Identity of nuclear high-mobility-group protein, HMG-1, and sulfoglucuronyl carbohydrate-binding protein, SBP-1, in brain.

High-mobility-group (HMG) proteins are a family of non-histone chromosomal proteins which bind to DNA. They have been implicated in multiple aspects of gene regulation and cellular differentiation. Sulfoglucuronyl carbohydrate binding protein, SBP-1, which is also localized in the neuronal nuclei, was shown to be required for neurite outgrowth and neuronal migration during development of the nervous system.

Expression and role of sulfoglucuronyl (HNK-1) carbohydrate and its binding protein SBP-1 in developing rat cerebral cortex.

Developmental expression of sulfoglucuronyl carbohydrate (SGC) and its binding protein, SBP-1 was studied in the rat cerebral cortex to understand their function. Between embryonic day (ED) 14-19, SBP-1 was strongly expressed in neurons of the ventricular zone and migrating neurons throughout the cortex. SBP-1 declined at birth and by postnatal day (PD) 3 only the latest arriving neurons in the most superficial segment of the cortical plate expressed SBP-1.

The beta 1,3-galactosyltransferase beta 3GalT-V is a stage-specific embryonic antigen-3 (SSEA-3) synthase.

We have previously reported the molecular cloning of beta1, 3-galactosyltransferase-V (beta3GalT-V), which catalyzes the transfer of Gal to GlcNAc-based acceptors with a preference for the core3 O-linked glycan GlcNAc(beta1,3)GalNAc structure. Further characterization indicated that the recombinant beta3GalT-V enzyme expressed in Sf9 insect cells also utilized the glycolipid Lc3Cer as an efficient acceptor. Surprisingly, we also found that beta3GalT-V catalyzes the transfer of Gal to the terminal GalNAc unit of the globoside Gb4, thereby synthesizing the glycolipid Gb5, also known as the stage-specific embryonic antigen-3 (SSEA-3).

Expression of sulfoglucuronyl (HNK-1) carbohydrate and its binding protein (SBP-1) in developing rat cerebellum.

Sulfoglucuronyl carbohydrate (SGC) is expressed on several glycoproteins of the immunoglobulin superfamily of cell-adhesion molecules. Developmental expression of SGC and its binding protein, SBP-1, was studied in the rat cerebellum by immunocytochemistry to understand the function of SBP-1 and the significance of its interaction with SGC. During early postnatal development (postnatal day (PD) 3-10) SBP-1 was strongly expressed in the granule neurons of the external and internal granule cell layers (EGCL and IGCL).

Interaction of sulfoglucuronyl (HNK-1) carbohydrate and its binding protein, SBP-1, in microexplant cultures of rat cerebellum.

Sulfoglucuronyl carbohydrate (SGC) is expressed on several neural cell-adhesion molecules and on glycolipids. SGC and its binding protein, SBP-1 are developmentally regulated in the nervous system and have been implicated in regulating neurite outgrowth and cell-cell recognition during neuronal cell migration. To elucidate the role of interaction between SGC and SBP-1, microexplant cultures of postnatal day 5 rat cerebellum were employed.

Expression of HNK-1 carbohydrate and its binding protein, SBP-1, in apposing cell surfaces in cerebral cortex and cerebellum.

Sulfoglucuronyl carbohydrate is the terminal moiety of neolacto-oligosaccharides, expressed on several glycoproteins of the immunoglobulin superfamily involved in cell-cell recognition and on two glycolipids. Sulfoglucuronyl carbohydrate is temporally and spatially regulated in the developing nervous system. It appears to be involved in neural cell recognition and in cell adhesion processes through its interaction with specific proteins on cell surfaces.

Restoration of synthesis of sulfoglucuronylglycolipids in cerebellar granule neurons promotes dedifferentiation and neurite outgrowth.

Sulfoglucuronyl carbohydrate (SGC) linked to the terminal moiety of neolacto-oligosaccharides is expressed in several glycoproteins of the immunoglobulin superfamily involved in neural cell-cell recognition as well as in two sulfoglucuronylglycolipids (SGGLs) of the nervous system. SGGLs and SGC-containing glycoproteins are temporally and spatially regulated during development of the nervous system. In the cerebellum, the expression of SGC, particularly that of SGGLs, is biphasic.

Characterization of a sulfoglucuronyl carbohydrate binding protein in the developing nervous system.

The developmentally regulated and stage-specifically expressed HNK-1 carbohydrate found on sulfoglucuronylglycolipids (SGGLs) and certain glycoproteins has been proposed to be involved in neural cell adhesion and recognition processes through its interaction with protein "receptors." We have isolated and purified a approximately 30-kDa SGGL-binding protein (SBP-1) from neonatal rat brain. SBP-1 specifically bound to SGGLs and sulfatide both in solid-phase immunobinding and high-performance thin-layer chromatography-immunooverlay assays.

N-Acetylglucosaminyl transferase regulates the expression of the sulfoglucuronyl glycolipids in specific cell types in cerebellum during development.

In the adult cerebellum, sulfoglucuronyl glycolipids (SGGLs) are specifically localized in Purkinje cells and their dendrites in the molecular layer. Other major cell types such as granule neurons and glial cells lack SGGLs. To explain the cell specific localization and the known biphasic expression of SGGLs, enzymic activities of four glycosyltransferases involved in the biosynthesis of SGGLs were studied in murine cerebellar mutants, in distinct cellular layers of rat cerebellum, and in isolated granule neurons during development.

Pathogenesis of corneal infection: binding of Pseudomonas aeruginosa to specific phospholipids.

Clinical isolates of Pseudomonas aeruginosa were examined for binding interactions with phospholipids of corneal epithelium. Thin-layer chromatography (TLC) of lipids extracted from corneal epithelia followed by staining with an ammonium molybdate spray reagent revealed three phospholipid components, PL1, PL2, and PL3. The chromatographic mobility of PL1 was similar to that of the phospholipid standards phosphatidylinositol (PI) and phosphatidylserine (PS), which were not well resolved from one other; PL2 and PL3 comigrated with the standards phosphatidylcholine and phosphatidylethanolamine, respectively.

Expression of neolactoglycolipids: sialosyl-, disialosyl-, O-acetyldisialosyl- and fucosyl- derivatives of neolactotetraosyl ceramide and neolactohexaosyl ceramide in the developing cerebral cortex and cerebellum.

The following neolacto glycolipids were identified and their developmental expression was studied in the rat cerebral cortex and cerebellum: Fuc alpha 1-3IIInLcOse4Cer,Fuc alpha 1-3VnLcOse6Cer and (Fuc)2 alpha 1-3III,3VnLcOse6Cer, as well as acidic glycolipids, NeuAc alpha 2-3IVnLcOse4Cer [nLM1], (NeuAc)2 alpha 2-3IVnLcOse4Cer [nLD1], O-acetyl (NeuAc)2 alpha 2-3IVnLcOse4Cer [OAc-nLD1] and their higher neolactosaminyl homologues NeuAc alpha 2-3VlnLcOse6Cer [nHM1] and (NeuAc)2 alpha 2-3VlnLcOse6Cer [nHD1]. These glycolipids were expressed in the cerebral cortex only during embryonic stages and disappeared postnatally. This loss was ascribed to the down regulation of the synthesis of the key precursor LcOse3Cer which is synthesized by the enzyme lactosylceramide: N-acetylglucosaminyl transferase.

Neolactoglycosphingolipids, potential mediators of corneal epithelial cell migration.

Cell migration is a fundamental process of wound repair in biological systems. In an attempt to identify plasma membrane glycoconjugates which mediate cell migration, migrating and nonmigrating rabbit corneal epithelia were analyzed for reactivity with monoclonal antibodies (mAbs) specific for unsubstituted N-acetyl-lactosamine (mAb 1B2), Le(x) (mAbs 7A and MMA), and sialyl Le(x) (mAb CSLEX1) carbohydrate chains of neolactoglycoconjugates. Immunohistochemical analysis indicated that regardless of whether the epithelia analyzed were from corneas of animals in vivo, corneas in organ culture, or cells in tissue culture, migrating cells stained intensely with mAb 1B2, whereas nonmigrating cells either did not stain or stained only weakly.

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.

Characterization and developmental expression of lactotriosylceramide:galactosyltransferase for the synthesis of neolactotetraosylceramide in the nervous system.

Neolactoglycolipids are derived from neolactotetraosylceramide (nLcOse4Cer). They are found during the embryonic and neonatal developmental periods in the rat cerebral cortex and disappear shortly after birth. These glycolipids are, however, abundant in the adult cerebellum.

N-acetylglucosaminyltransferase regulates the expression of neolactoglycolipids including sulfoglucuronylglycolipids in the developing nervous system.

Lactosylceramide N-acetylglucosaminyltransferase (GlcNac-Tr) in the synthesis of lactotriosylceramide (LcOse3Cer) was characterized in the nervous system. The microsomal membrane GlcNAc-Tr required a divalent metal ion, preferably Mn2+, and a nonionic detergent. The pH optimum was around 7.

Rostrocaudal expression of antibody HNK-1-reactive glycolipids in mouse cerebellum: relationship to developmental compartments and leaner mutation.

Sulfoglucuronylglycolipids (SGGLs) and glycoproteins, reacting with monoclonal antibody HNK-1, are developmentally and spatially regulated in the mammalian cortex and cerebellum. It has been proposed that the HNK-1 carbohydrate epitope is involved in intercellular adhesion and cell-cell interactions. Biochemical analysis and immunocytochemical localization of SGGLs and other neolacto series glycolipids were studied in the leaner mutant mouse cerebellum, where a slow and progressive rostral to caudal degeneration occurs with a gradual loss of both granule cells and Purkinje cells.

Characterization and developmental expression of a novel sulfotransferase for the biosynthesis of sulfoglucuronyl glycolipids in the nervous system.

Sulfoglucuronyl glycolipids (SGGLs) are temporally and spatially regulated molecules in the developing nervous system. A novel sulfotransferase (ST) from rat brain which catalyzes the terminal step in the biosynthesis in vitro of SGGLs is described. The enzyme catalyzes a transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate to a hydroxyl group on carbon 3 of the terminal glucuronyl residue in IV3 beta-glucuronyl neolactotetraosylceramide (GlcAnLcOse4Cer) and VI3 beta-glucuronyl neolactohexaosylceramide (GlcAnLcOse6Cer) to form 3-sulfated glucuronyl glycolipids.

Temporal expression of HNK-1-reactive sulfoglucuronyl glycolipid in cultured quail trunk neural crest cells: comparison with other developmentally regulated glycolipids.

Monoclonal antibody HNK-1 is an important marker for embryonic neural crest cells and some of their differentiated derivatives. We have identified 3-sulfoglucuronylneolactotetraosylceramide (SGGL-1) as one of the HNK-1 antigens present in cultures of trunk neural crest cells. This lipid was present at 2 days in vitro and increased in amount with time in culture.