Signal Transduction Through Prion Protein

• DOI: 10.1126/science.289.5486.1925
• Publication Date: 2002-07-27T09:37:46Z
• Authors: S. Mouillet-Richard; M. Ermonval; C. Chebassier; J. L. Laplanche; S. Lehmann; J. M. Launay; O. Kellermann
• Keywords: Neurons; 0301 basic medicine; Caveolin 1; Membrane Proteins; Cell Differentiation; Proto-Oncogene Proteins c-fyn; Caveolins; Cell Compartmentation; Enzyme Activation; Mice; 03 medical and health sciences; Proto-Oncogene Proteins; Animals; PrPC Proteins; Signal Transduction

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.