Activity-dependent mobilization of the adhesion molecule polysialic NCAM to the cell surface of neurons and endocrine cells.

Kiss, József Zoltán; Wang, Cheng; Olive, Sylviane; Rougon, Geneviève; Láng, J.; Baetens, D.; Harry, Daniela; Pralong, William

doi:10.1002/j.1460-2075.1994.tb06862.x

Cited by 144 publications

(112 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, our data suggest that an increase in the homophilic interactions of NCAM180 or its binding to the spectrin cytoskeleton can also promote immobilization of NCAM180 in activated synapses. In agreement with this idea, synaptic activity is accompanied by cell surface delivery of NCAM from intracellular organelles (52) and may therefore increase its homophilic interactions. Clustering of NCAM induces the assembly of the spectrin meshwork (25,35), which in turn may promote the retention of NCAM180 at activated synapses.…”

Section: Discussionsupporting

confidence: 52%

Immobilized Pool of NCAM180 in the Postsynaptic Membrane Is Homeostatically Replenished by the Flux of NCAM180 from Extrasynaptic Regions

Leshchyns’ka

Tanaka

Schachner

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Homeostatic mechanisms maintaining high levels of adhesion molecules in synapses over prolonged periods of time remain incompletely understood. We used fluorescence recovery after photobleaching experiments to analyze the steady state turnover of the immobile pool of green fluorescent protein-labeled NCAM180, the largest postsynaptically accumulating isoform of the neural cell adhesion molecule (NCAM). We show that there is a continuous flux of NCAM180 to the postsynaptic membrane from nonsynaptic regions of dendrites by diffusion. In the postsynaptic membrane, the newly delivered NCAM180 slowly intermixes with the immobilized pool of NCAM180. Preferential immobilization and accumulation of NCAM180 in the postsynaptic membrane is reduced after disruption of the association of NCAM180 with the spectrin cytoskeleton and in the absence of the homophilic interactions of NCAM180 in synapses. Our observations indicate that the homophilic interactions and binding to the cytoskeleton promote immobilization of NCAM180 and its accumulation in the postsynaptic membrane. Flux of NCAM180 from extrasynaptic regions and its slow intermixture with the immobile pool of NCAM180 in the postsynaptic membrane may be important for the continuous homeostatic replenishment of NCAM180 protein at synaptic contacts without compromising the long term synaptic contact stability.Neurons are assembled into circuits via specialized contacts, called synapses, that are essential for information processing, learning, and storage in the brain. Synapses are stable long lasting structures (1-3). This stability is at least partially rendered by a number of cell adhesion molecules accumulating in the pre-and postsynaptic membranes (4 -9). During development, cell adhesion molecules are delivered to nascent synapses in intracellular organelles or as cell surface aggregates (10 -12). A similar type of quantal delivery of adhesion molecules has been also observed during induction of long term potentiation (13). Long lasting stability of synapses (months or years), however, suggests that synaptic pools of cell adhesion molecules (protein life time hours or days) have to be also homeostatically and continuously replenished over prolonged periods of time without compromising synapse stability and composition. Mechanisms of such replenishment remain poorly understood.Among synaptic adhesion molecules, the neural cell adhesion molecule (NCAM), 2 a member of the immunoglobulin superfamily of adhesion molecules, was shown to be involved in mechanical stabilization of interneuronal contacts and their transformation into synapses (12,14). In mice, deficiency in NCAM results in impaired long term potentiation, increased aggression and anxiety, deficits in spatial learning, and exploratory behavior (15-21). In humans, genetic variations in the NCAM gene have been reported to confer risk factors associated with bipolar affective disorders and schizophrenia (22)(23)(24). The largest isoform of NCAM, NCAM180, accumulates in the postsynaptic membrane and recruits the s...

show abstract

Section: Discussionsupporting

confidence: 52%

Immobilized Pool of NCAM180 in the Postsynaptic Membrane Is Homeostatically Replenished by the Flux of NCAM180 from Extrasynaptic Regions

Leshchyns’ka

Tanaka

Schachner

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Consistent with this finding, NCAM knockout mice and mice treated with the enzyme Endo-N also were found to be characterized by a learning deficit (5,8). As PSA-NCAM is expressed at the synapse and because its expression is affected by neuronal and synaptic activity (3,9), it has been proposed that PSA-NCAM could represent an important modulator of activity-induced plasticity in the hippocampus (7).…”

mentioning

confidence: 64%

“…Taken together, these results support the hypothesis that one important role of PSA-NCAM could be to enhance or facilitate BDNF activation of its receptor, and thereby sensitize pyramidal cells to the action of the growth factor. Because PSA-NCAM is expressed at the cell surface and at synapses in an activity-dependent manner (3,9), this mechanism could represent a way to amplify or selectively enhance the action of BDNF at active sites or active synapses. This might be particularly important for mechanisms of synaptic plasticity and LTP where the synaptic changes exhibit some input specificity.…”

Section: Discussionmentioning

confidence: 99%

Brain-derived neurotrophic factor restores long-term potentiation in polysialic acid-neural cell adhesion molecule-deficient hippocampus

Michelet

Djebbara-Hannas²,

Jourdain³

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

193

125

View full text Add to dashboard Cite

The neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) contribute to long-term potentiation (LTP) in the CA1 hippocampus. Here we report that the deficient LTP found in slices prepared from NCAM knockout mice and in organotypic slice cultures treated with Endo-N, an enzyme that cleaves the PSA moiety of NCAM, can be rescued by brain-derived neurotrophic factor (BDNF). This effect is not reproduced by nerve growth factor, but can be obtained with high concentrations of NT4/5. The effect of BDNF cannot be accounted for by modifications of N-methyl-D-aspartate receptor-dependent responses or of high-frequency bursts. PSA-NCAM, however, could directly interact with BDNF. Exogenous application of PSA residues or recombinant PSA-NCAM also prevents LTP. Furthermore trkB phosphorylation, and thus BDNF signaling, is reduced in both NCAM knockout mice and Endo-N-treated slice cultures. These results suggest that one action of PSA-NCAM could be to sensitize pyramidal neurons to BDNF, thereby modulating activity-dependent synaptic plasticity

show abstract

“…The recent accumulation of evidence suggests a link between calcium and polysialic acid interactions during neuronal development: Calcium ions have been shown to be involved in the regulation of polysialylation (Brusés and Rutishauser, 1998) and aggregation properties of NCAM (Rouiller et al, 1990;Kiss et al, 1994). Calcium entry is also shown to regulate NCAM isoform expression and polysialylation in the developing muscle (Rafuse and Landmesser, 1996).…”

Section: Divalent Cationsmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Activity-dependent mobilization of the adhesion molecule polysialic NCAM to the cell surface of neurons and endocrine cells.

Cited by 144 publications

References 59 publications

Immobilized Pool of NCAM180 in the Postsynaptic Membrane Is Homeostatically Replenished by the Flux of NCAM180 from Extrasynaptic Regions

Immobilized Pool of NCAM180 in the Postsynaptic Membrane Is Homeostatically Replenished by the Flux of NCAM180 from Extrasynaptic Regions

Brain-derived neurotrophic factor restores long-term potentiation in polysialic acid-neural cell adhesion molecule-deficient hippocampus

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

Contact Info

Product

Resources

About