Characterization of a Sulfoglucuronyl Carbohydrate Binding Protein in the Developing Nervous System

Nair, S.M; Jungalwala, Firoze B.

doi:10.1046/j.1471-4159.1997.68031286.x

Cited by 35 publications

(57 citation statements)

References 35 publications

(55 reference statements)

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“…S100B functions as a stable dimer (13,15) and although amphoterin also has a tendency to form dimers and multimers (6), it probably has to be attached to a substrate in order to effectively activate the receptor. Amphoterin is known to bind to some other cell surface components in addition to RAGE, including syndecan-1 (47), receptor-type tyrosine phosphatase ␤/ (48), and some sulfated glycolipids (49). How these molecules are involved in this whole scenario remains to be seen.…”

Section: Discussionmentioning

confidence: 99%

Coregulation of Neurite Outgrowth and Cell Survival by Amphoterin and S100 Proteins through Receptor for Advanced Glycation End Products (RAGE) Activation

Huttunen¹,

Kuja-Panula²,

Sorci³

et al. 2000

Journal of Biological Chemistry

536

532

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Amphoterin is a protein enhancing process extension and migration in embryonic neurons and in tumor cells through binding to receptor for advanced glycation end products (RAGE), a multiligand transmembrane receptor. S100 proteins, especially S100B, are abundantly expressed in the nervous system and are suggested to function as cytokines with both neurotrophic and neurotoxic effects. However, the cell surface receptor for the cytokine function of S100B has not been identified. Here we show that two S100 family proteins, S100B and S100A1, activate RAGE in concert with amphoterin inducing neurite outgrowth and activation of transcription factor NF-B. Furthermore, activation of RAGE by amphoterin and S100B promotes cell survival through increased expression of the anti-apoptotic protein Bcl-2. However, whereas nanomolar concentrations of S100B induce trophic effects in RAGE-expressing cells, micromolar concentrations of S100B induce apoptosis in an oxidant-dependent manner. Both trophic and toxic effects are specific for cells expressing full-length RAGE since cells expressing a cytoplasmic domain deletion mutant of RAGE are unresponsive to these stimuli. These findings suggest that activation of RAGE by multiple ligands is able to promote trophic effects whereas hyperactivation of RAGE signaling pathways promotes apoptosis. We suggest that RAGE is a signal-transducing receptor for both trophic and toxic effects of S100B.Receptor for advanced glycation end products (RAGE) 1 is a member of the immunoglobulin superfamily of cell surface proteins interacting with a range of ligands, including advanced glycation end products (AGE) (1), amyloid-␤ peptide (2), amphoterin (3), and members of the S100 family (4). Whereas AGE and amyloid-␤ peptide are known to induce cellular perturbation through their interaction with RAGE, amphoterin and S100 proteins are considered to be physiological ligands of RAGE in migratory and inflammatory cellular responses. However, mechanistically it is not understood how RAGE-mediated cellular responses can change from trophic to toxic.Amphoterin is a heparin-binding, neurite outgrowth-promoting protein that is highly expressed in embryonic and transformed cells (5-7). RAGE has been shown to mediate neurite outgrowth of cortical neurons and neuroblastoma cells on amphoterin-coated substrates (3, 8). Furthermore, amphoterin and RAGE co-localize at the leading edge of advancing neurites in the developing central nervous system (3). Our previous results suggesting that amphoterin might be a more general regulator of cell migration (reviewed in Ref. 9) are supported by the recent findings showing that blockade of amphoterin-RAGE interaction decreases invasion and growth of both implanted and spontaneously developing tumors (10). S100B is a member of a multigenic family of Ca 2ϩ -regulated proteins of the EF-hand type that has been implicated in the regulation of protein phosphorylation, the dynamics of cytoskeleton constituents, the cell cycle, and some enzymes (11,12). S100B is abundant in the n...

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Section: Discussionmentioning

confidence: 99%

Coregulation of Neurite Outgrowth and Cell Survival by Amphoterin and S100 Proteins through Receptor for Advanced Glycation End Products (RAGE) Activation

Huttunen¹,

Kuja-Panula²,

Sorci³

et al. 2000

Journal of Biological Chemistry

536

532

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“…Alternatively the HNK-1 carbohydrate itself may be involved in LTP via interaction with binding proteins (receptors) on the cell surface or in the cell matrix. Several HNK-1 carbohydrate-binding proteins have been identified, such as laminin, selectins, SBP-1, and brevican (25)(26)(27)(28). However, the association of these receptors or binding proteins with LTP has not been proved.…”

Section: Discussionmentioning

confidence: 99%

Mice Deficient in Nervous System-specific Carbohydrate Epitope HNK-1 Exhibit Impaired Synaptic Plasticity and Spatial Learning

Yamamoto¹,

Oka²,

Inoue³

et al. 2002

Journal of Biological Chemistry

142

114

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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). We generated mice with a targeted deletion of the GlcAT-P gene. 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. This is the first evidence that the loss of a single non-reducing terminal carbohydrate residue attenuates brain higher functions.Glycosylation is a major post-translational protein modification, especially for cell surface proteins, which play important roles in a variety of cellular functions including recognition and adhesion. In the last decade, a number of glycosyltransferase genes and related genes have been cloned. Targeted deletion of these genes revealed the roles of cell surface glycans in the modulation of cellular interactions, particularly in the immune system (1, 2). We have been interested in the roles of a neuralspecific carbohydrate, the HNK-1 carbohydrate, which is expressed on glycoproteins as well as on glycolipids and is postulated to be associated with cell adhesion, migration, and neurite outgrowth (3-5). The epitope is a sulfated trisaccharide, HSO 3 -3GlcA␤1-3Gal␤1-4GlcNAc (6, 7), and the inner structure, Gal␤1-4GlcNAc, is commonly found on various glycoproteins and glycolipids. To elucidate the roles of the HNK-1 carbohydrate more clearly, we cloned two different glucuronyltransferases (GlcAT-P and GlcAT-S) 1 (8 -11), which are key enzymes in the biosynthesis of the HNK-1 carbohydrate epitope (12,13). In this study, we generated mice with a targeted deletion of the GlcAT-P gene and demonstrated clearly that the HNK-1 carbohydrate is in fact required for higher functions of the brain. EXPERIMENTAL PROCEDURESTargeted Disruption of the GlcAT-P Gene-Cloning of the genomic clones of the 129/Sv mouse GlcAT-P gene was described previously (10). Construction of the targeting vector is schematically represented in Fig. 1A. The neomycin resistance gene cassette in vector pPGKneobpA (14) and diphtheria toxin A (DT-A) gene cassette in vector pMC1DT-A (15) were used as positive and a negative selection markers, respectively. The targeting vector was transfected into E14-1 embryonic stem (ES) cells (16) by electroporation. Two ES clones among 525 tested revealed the desired homologous recombination (13C-2 and 22D-5). To generate chimeric mice, both clones were aggregated with C57BL/6 ϫ BDF1 8-cell-stage embryos, and the embryos were transferred into the uteri of pseudopregnant mice. Both clones gave rise to germline chimeras. Mice heterozygous for the mutation were obtained by cross-breeding of the chimeras with C57BL/6 mice. The heterozygotes were further backcrossed with C57BL/6 mice for more than eight generations, and the resulting heterozygous mutants were interbred ...

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“…In support of the first possibility, the galactolipids, particularly sulfatide, bind various cell adhesion proteins (Vos et al, 1994) including tenascin family molecules (Crossin and Edelman, 1992;Pesheva et al, 1997) and laminin (Roberts and Ginsburg, 1988). Moreover, several studies have recently established a precedent that certain axon-glial interactions may involve protein-lipid binding (White and Schnaar, 1994;Yang et al, 1996;Nair and Jungalwala, 1997). Nevertheless, specific axolemma binding partners for the myelin galactolipids remain to be identified.…”

Section: Mechanismmentioning

confidence: 99%

Myelin galactolipids: Mediators of axon-glial interactions?

Popko

2000

Glia

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The precise alignment of myelin segments along the length of the axon is essential for the saltatory propagation of an electrical impulse. Furthermore, node of Ranvier formation and function are dependent on the proper interactions between myelinating glial cells and the axon. Nevertheless, the molecules that regulate the placement and association of myelinating cells with axons remain largely unidentified. Recently, however, the analysis of mutant mice incapable of synthesizing the galactolipids of myelin has revealed defects in these processes. The galactolipid‐deficient mice display alterations in the spacing of internodal segments along the axon: large unmyelinated gaps are common and overlapping myelin segments are observed. Moreover, the normal tight association between the lateral loops of the myelinating cell and the axonal membrane at the paranode region is also disrupted in these animals. Strikingly, there is a complete absence of transverse bands at the axon‐glial junction, with the lateral loops frequently turning away from the axon. These data indicate that the galactolipids play an essential role in axon‐glial interactions and node of Ranvier formation. GLIA 29:149–153, 2000. © 2000 Wiley‐Liss, Inc.

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Characterization of a Sulfoglucuronyl Carbohydrate Binding Protein in the Developing Nervous System

Cited by 35 publications

References 35 publications

Coregulation of Neurite Outgrowth and Cell Survival by Amphoterin and S100 Proteins through Receptor for Advanced Glycation End Products (RAGE) Activation

Coregulation of Neurite Outgrowth and Cell Survival by Amphoterin and S100 Proteins through Receptor for Advanced Glycation End Products (RAGE) Activation

Mice Deficient in Nervous System-specific Carbohydrate Epitope HNK-1 Exhibit Impaired Synaptic Plasticity and Spatial Learning

Myelin galactolipids: Mediators of axon-glial interactions?

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