Signal Transduction Through Prion Protein

Abstract

The cellular prion protein PrPc is a glycosylphosphatidylinositol-anchored cell-surface protein whose biological function is unclear. We used the murine 1C11 neuronal differentiation model to search for PrPc-dependent signal transduction through antibody-mediated cross-linking. A caveolin-1-dependent coupling of PrPc to the tyrosine kinase Fyn was observed. Clathrin might also contribute to this coupling. The ability of the 1C11 cell line to trigger PrPc-dependent Fyn activation was restricted to its fully differentiated serotonergic or noradrenergic progenies. Moreover, the signaling activity of PrPc occurred mainly at neurites. Thus, PrPc may be a signal transduction protein.

New insights into cellular prion protein (PrPc) functions: The “ying and yang” of a relevant protein

“…In this sense, we would like to remark two sets of studies with opens the notion of PrP c as a signaling molecule. In the first, using PrP c aggregation strategies, Mouillet-Richard and coworkers reported that PrP c -mediated signaling by P59Fyn kinase modulates cell survival in 1C11 cell line (Mouillet-Richard et al, 2000;Santuccione et al, 2005). This data is crucial since it linked the survival properties of PrP c to a specific signaling pathway.…”

Misfolding of the prion protein: linking biophysical and biological approaches

“…Peptides corresponding to internal sequences of PrP (109-122 and 109-141) were shown to interact in vitro with apolipoprotein E [6]. Receptor proteins playing a role in signal transduction were found to interact directly such as laminin receptor [128] or indirectly like kinase Fyn [79], with internal [27,31] cell machinery. α-and β-tubulin and N-CAM, cytoskeleton or close to cytoskeleton proteins were also found to interact with PrP.…”

Des maladies à prions à la maladie d’Alzheimer

“…C'est la conversion transconformationnelle d'une protéine endogène de l'hôte, la protéine prion cellulaire (PrP C ), en PrP Sc qui est à l'origine des maladies à prions. La PrP C est une sialoglycoprotéine ancrée à la membrane plasmique via un groupement glycosylphosphatidylinositol, qui, en tant que récepteur ou corécepteur, joue un rôle multifacette dans la signalisation cellulaire [1,2]. Le clivage de la PrP C par des -sécrétases, entre les acides aminés 111 et 112, libère une forme amino-terminale tronquée qui n'est plus convertible en PrP Sc et exerce un effet dominant négatif sur la réplica-tion de la PrP Sc [3].…”