The cellular prion protein PrPc is a glycosylphosphaltidylinositol-anchored
cell-surface protein whose biological function is unclear: We used the mur
ine 1C11 neuronal differentiation model to search for PrPc-dependent signal
transduction through antibody-mediated cross-linking. A caveolin-1-depende
nt 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 tri
gger PrPc-dependent Fyn activation was restricted to its fully differentiat
ed serotonergic or noradrenergic progenies. Moreover, the signaling activit
y of PrPc occurred mainly at neurites. Thus, PrPc may be a signal transduct
ion protein.