Signal Transduction Through Prion Protein

Abstract

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