Occurrence of α2–8 linked polysialosyl units in a neural cell adhesion molecule

Finne, Jukka; Finne, Ulla; Deagostini‐Bazin, Hermine; Goridis, Christo

doi:10.1016/0006-291x(83)91490-0

Cited by 397 publications

(229 citation statements)

References 13 publications

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“…Thus, co-operative binding could cause the linear region observed in the Scatchard plot of MenB, since an extended 200-mer is generally thought to span about 1200 Å. Actually, this paradigm could reflect the in vivo situation more closely as several adjacent PSA-chains are present both in NCAM N-glycosylation sites and bacterial PSA capsules (Finne et al, 1983a;Jennings et al, 1984). Although, measuring polyvalent affinities is an established method (Mammen et al, 1998), additional information could have been obtained by immobilizing the polysaccharides on the chip and using antibodies and Fab-fragments as analytes.…”

Section: Psa-ab Interactionmentioning

confidence: 99%

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High affinity binding of long-chain polysialic acid to antibody, and modulation by divalent cations and polyamines

Häyrinen¹,

Haseley²,

Talaga³

et al. 2002

Molecular Immunology

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Long-chain polysialic acid (PSA) is expressed on the vertebrate neural cell adhesion molecule (NCAM) during neuronal plasticity. Its structural similarity to the capsular PSAs of some pathogenic bacteria has hampered the development of polysaccharide vaccines against meningitis. The antibodies formed during immunization require a long epitope for binding, and cross-react with host tissue PSA. The nature of the epitope and possible external effectors involved are still unclear. We have evaluated the interaction of PSA with its antibody mAb735 by surface plasmon resonance. The influences of PSA chain length, pH, temperature, ionic environment, and polyamines were also determined.The antibody binding affinity was found to dramatically increase with PSA chain length. A sub-nanomolar dissociation constant (K D = 8.5 × 10 −10 M) was obtained for the binding of very long chain native MenB polysaccharides (∼200 Neu5Ac-residues). Colominic acid from Escherichia coli K1 (∼100 residues) and shorter polymers exhibited progressively weaker affinities. The antibody also bound tightly (K D ∼ 5 × 10 −9 M) to polysialylated glycopeptides from human embryonal brain. The effects of pH and ionic strength suggested that the interaction is largely electrostatic. Ca 2+ and Mn 2+ ions promoted the observed surface plasmon resonance response in a concentration dependent fashion. Spermine increased the response in a similar way. Our results suggest that divalent cations and polyamines may play significant role in the regulation of the PSA epitope presentation in vivo.

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Section: Psa-ab Interactionmentioning

confidence: 99%

“…It is present in the N-glycans of neural cell adhesion molecules (NCAM) of vertebrate cells (Finne et al, 1983a) …”

Section: Introductionmentioning

confidence: 99%

High affinity binding of long-chain polysialic acid to antibody, and modulation by divalent cations and polyamines

Häyrinen¹,

Haseley²,

Talaga³

et al. 2002

Molecular Immunology

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“…The binding site for 5A5 is removed with treatment of NCAM with endoneuraminidase N which specifically cleaves sialic acid polymers in chains of 8 or longer (Vimr et al, 1984). NCAM is likely to be the major glycoprotein in chicken embryos with this particular carbohydrate construct (Finne 1982;Finne et al, 1983;Vimr et al, 1984;Rougon et al, 1986;Regan 1991).…”

Section: Experimental Procedures Antibody Reagentsmentioning

confidence: 99%

“…The polysialylation of NCAM is of particular importance because of its effect on NCAM homophilic binding (Hoffman and Edelman 1983;Sadoul et al, 1983) and on cell-cell interactions in general . This carbohydrate moiety is composed of a-2-%linked sialic acids in long chains (Finne et al, 1983) which can represent 30% of the weight of NCAM (Hoffman and Edelman, 1983). The amount of polysialic acid (PSA) on NCAM varies with tissue and developmental stage with the general pattern being low polysialylation followed by high polysialylation in developing systems and low polysialylation in mature systems (Sunshine et al, 1987;Chuong and Edelman, 1984).…”

Section: Introductionmentioning

confidence: 99%

Cardiac expression of polysialylated NCAM in the chicken embryo: Correlation with the ventricular conduction system

Watanabe

Timm

Fallah‐Najmabadi

1992

Developmental Dynamics

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The neural cell adhesion molecule (NCAM) and its polysialic acid moeity (PSA) affect cellular interactions during the development of the nervous system and skeletal muscle. NCAM has also been identified in the embryonic heart of various species including humans. However, knowledge regarding the role of NCAM and its function-modulating PSA in cardiogenesis is limited. The distribution of NCAM and its PSA in the ventricular myocardium of chicken embryos was determined by indirect immunofluorescence staining. The NCAM polypeptide was found throughout the cardiac myocardium. In contrast PSA was located in discrete regions in stage 20 to 44 embryos (during and after septation). Myocardium at the subendocardial regions of the atrioventricular canal and ventricular trabeculae were PSA positive by stage 20. At later stages, transverse sections of the postseptation heart just below the level of the atrioventricular interface revealed a PSA-positive bundle of myocardium in the septum. This bundle was continuous with two branches at a more apical level which in turn were continuous with the PSA-positive subendocardial myocardium lining the left and right ventricles. This pattern of PSA in the myocardium was similar to that of the ventricular conduction system configuration defined in the adult heart. Electron micrographs of the subendocardium of the ventricular septum revealed PSA positivity on myofibril-containing cells with the ultrastructural location of Purkinje fibers. At later stages (3544) a subset of cells within PSA-positive regions was stained by an antibody against an isoform of the myosin heavy chain found in adult Purkinje fibers. These cells and surrounding tissue lacked PSA in the adult heart. Thus polysialylated NCAM may be modulating cell-cell interactions during the development of the ventricular conduction system. 0 1992 Wiley-Liss, Inc.

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“…Polysialic acid (PSA) is another post-translational modification consisting of a homopolymer of a(2,8) linked sialic acid, which plays a critical role in regulating neural development and tumor progression [15]. Dramatically, concomitant with a marked reduction of polysialylation detected by antipoly-sialylation antibody, we found that the transcript levels of ST8Sia II/STX were significantly reduced after deletion of GnT-Va, while the level of ST8Sia IV/PST was very low.…”

Section: Discussionmentioning

confidence: 78%

Loss of expression of N‐acetylglucosaminyltransferase Va results in altered gene expression of glycosyltransferases and galectins

et al. 2008

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We isolated mouse embryo fibroblasts (MEFs) from N-acetylglucosaminyltransferase Va (GnT-Va) knockout mice and studied the effects of loss of expression of GnT-Va on asparagine-linked glycans (N-glycan) synthesis and the gene expression of groups of glycosyltransferases and galectins. Loss of GnT-Va expression caused aberrant expression of several N-glycan structures, including N-linked b(1,6) branching, poly-N-lactosamine, bisecting N-acetylglucosamine (GlcNAc) and sialic acid. Using quantitative reverse transcriptase-PCR (qRT-PCR), altered gene expression of several groups of glycosyltransferases and galectins was observed in GnT-Va null MEFs, supporting the observed changes in N-glycan structures. These results suggest that genetic disruption of GnT-Va ultimately resulted in altered MEFs gene expression and decreased tumor progression associated with loss of GnT-Va observed may result in part from a combination of effects from these altered gene expressions.

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Occurrence of α2–8 linked polysialosyl units in a neural cell adhesion molecule

Cited by 397 publications

References 13 publications

High affinity binding of long-chain polysialic acid to antibody, and modulation by divalent cations and polyamines

High affinity binding of long-chain polysialic acid to antibody, and modulation by divalent cations and polyamines

Cardiac expression of polysialylated NCAM in the chicken embryo: Correlation with the ventricular conduction system

Loss of expression of N‐acetylglucosaminyltransferase Va results in altered gene expression of glycosyltransferases and galectins

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