Servizio Comunitario di Informazione in materia di Ricerca e Sviluppo - CORDIS

Effect of PrP conversion on signal transduction

We have used a neuroblastoma cell model to investigate the involvement of PrP in cell adhesion. Interestingly, cells overexpressing PrP exhibit increased cation-independent aggregation. This suggest that PrP acts as an intercellular adhesion molecule and a cell surface ligand or receptor. In addition, we demonstrated the 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.

Consequences of the cis and trans interaction between NCAM and PrP for transmissible and non-transmissible prion diseases, leading to infectious propagation of the mutation with its loss-of-function or gain-of-function respectively, will need to be viewed in the context of PrP interacting heterophilically with other molecules, such as NCAM. We have shown previously and in this study that homophilic trans-interactions between PrPC molecules are not involved in neurite outgrowth (Chen et al., 2003). Interestingly, the incubation period of the scrapie conformer of prion protein (PrPSc) is not altered in NCAM-/- mice to NCAM+/+ mice, suggesting that NCAM does not affect PrPSc formation (Schmitt-Ulms et al., 2001). Also, it has been excluded that neurodegeneration occurs because of PrP deficiency (Mallucci et al., 2002). It is thus conceivable that interactions between PrP and NCAM are altered by accumulation of PrPSc in the diseased nervous system. This would lead to a consequent alteration in the activation of PrPC-mediated and NCAM-induced fyn signalling pathway activation.

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