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FP5

PRP AND NEURODEGENER Report Summary

Project ID: QLG3-CT-2001-02353
Funded under: FP5-LIFE QUALITY
Country: France

Role of PrP in cell adhesion and neuritogenesis 2

We have used a neuroblastoma cell model to investigate the involvement of PrP in cell adhesion. Incubation of single cell suspension induced cell adhesion and formation of cell aggregates. Interestingly, cells overexpressing PrP exhibit increased cation-independent aggregation. Aggregation was reduced after phosphatidylinositol-specific phospholipase C release of the protein and by preincubation of cells with an antibody raised against the N-terminal part of PrPC. Our paradigm allows the study of the function of PrP as an intercellular adhesion molecule and a cell surface ligand or receptor.

We also participated with Partner 5, to the set up of a new experimental model where recombinant prion protein was substrate-coated to test its effect on neurite outgrowth on primary culture from early postnatal mouse brain. It was thus shown that PrP could significantly promote neurite outgrowth through a pathway involving src family kinase as well as ERK. In addition we showed that PrP bears the HNK-1 glycanic epitope which represents an additional argument to consider that PrP can be considered as a cell adhesion molecule.

Ref:
Mangé A., Milhavet O., Umlauf D., Harris D.A. et Lehmann S. (2002) PrP-dependent cell adhesion in N2a neuroblastoma cells FEBS Letters 514, 159-62

Chen S., Mangé A, Dong L, Lehmann S. & Schachner M. (2003) Prion protein as trans-interacting partner for neurons is involved in neurite outgrowth and neuronal survival. Mol Cell Neurosci. 2003 2:227-33.

Contact

Sylvain LEHMANN, (Head of Group)
Tel.: +33-499619931
Fax: +33-499619901
E-mail
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