Structure, biosynthesis and function of the developmentally regulated polysialic acid moiety of the neural cell adhesion molecule NCAM

• Unité de recherche: PCRD EU
• Numéro de projet: 96.0339a
• Titre du projet anglais: Structure, biosynthesis and function of the developmentally regulated polysialic acid moiety of the neural cell adhesion molecule NCAM

Mots-clé (Anglais)

Adhesion molecules; NCAM; polysialic acid; synaptic plasticity

Autre Numéro de projet (Anglais)

EU project number: BIO4CT960730

Programme de recherche (Anglais)

EU-programme: 4. Frame Research Programme - 4.1 Biotechnology

Description succincte (Anglais)

See abstract

Partenaires et organisations internationales (Anglais)

Gerardy-Schahn (D), Finne (FIN),Schachner (D), Goridis (F)

Résumé des résultats (Abstract) (Anglais)

Involvement of NCAM and PSA-NCAM in synaptic plasticity.
The neural cell adhesion molecule NCAM and its polysialylated form PSA-NCAM have been implicated in various aspects of neural and synaptic plasticity. Work carried out in hippocampal slices and slice cultures showed that interference with NCAM or PSA-NCAM by elimination of the NCAM molecule or using antibodies or a neuroaminidase (Endo-N) that selectively removes PSA from NCAM, results in a deficient LTP in the CA1 hippocampus (Lüthi et al., 1994; Muller et al., 1996). The mechanisms through which NCAM and PSA-NCAM contribute to synaptic plasticity remains however unclear. To address this issue, we investigated the possibility of an interaction between PSA-NCAM and signaling cascades mediated by growth factors. We found that application of BDNF to slices prepared from NCAM deficient mice rescued the deficient LTP. This effect was not reproduced by NGF, but could be obtained with high concentrations of NT-4/5 (Muller et al., 2000). In addition, we found that the level of phosphorylation of trkB, the receptor for BDNF was significantly reduced in NCAM deficient mice, thereby suggesting a deficient activation of the BDNF signaling cascade in these transgenic animals. These results were interpreted as suggesting a possible interaction between PSA-NCAM and BDNF signaling (Muller et al., 2000).
Since both NCAM, PSA-NCAM and BDNF regulate cell interactions and could contribute to a morphological remodelling of synapses, we also analysed whether they could be required for the structural plasticity of synapses found after LTP induction. In recent work, we showed that induction of LTP results in a sequence of morphological changes starting with a transient increase in the proportion of perforated synapses followed by a process of spine duplication (Toni et al., 1999). To determine whether PSA-NCAM is required for this structural plasticity, we analysed the effect of PSA removal by Endo-N treatment on the occurrence of perforated synapses. Morphometric analyses were carried out 30 min after high frequency stimulation in control and Endo-N treated slice cultures. The results indicate that removal of PSA from NCAM prevents LTP induction as well as the increase in the proportion of perforated synapses observed at that time point. Thus PSA-NCAM contributes both to functional and structural forms of synaptic plasticity.

Références bases de données (Anglais)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 96.0339a