The cellular prion protein (PrPC), encoded by the PRNP gene, is a ubiquitous glycoprotein, which is highly expressed in the brain. This protein, mainly known for its role in neurodegenerative diseases, is involved in several physiological processes including neurite outgrowth. By using a novel focal stimulation technique, we explored the potential function of PrPC, in its soluble form, as a signaling molecule. Thus, soluble recombinant prion proteins (recPrP) encapsulated in micro-vesicles were released by photolysis near the hippocampal growth cones. Local stimulation of wild-type growth cones with full-length recPrP induced neurite outgrowth and rapid growth cone turning towards the source. This effect was shown to be concentration dependent. Notably, PrPC-knockout growth cones were insensitive to recPrP stimulation, but this property was rescued in PrP-knockout growth cones expressing GFP–PrP. Taken together, our findings indicate that recPrP functions as a signaling molecule, and that its homophilic interaction with membrane-anchored PrPC might promote neurite outgrowth and facilitate growth cone guidance.
The authors declare no competing or financial interests.
D.C. and G.L. conceived the project. L.A., D.C. and G.L. designed the experiments. D.C. and L.A. developed the local delivery setup and imaging protocols. L.A. performed local delivery and immunofluorescence experiments. L.A., D.C. and G.L. analyzed the data. X.T.A.N., contributed to cell culture. G.G. and T.H.T. contributed to protein production. I.G.R. performed western blot experiments. L.A. and E.D. performed STED experiments and analysis. V.Č.Š. provided the EB8 antibody and supervised the related experiments. L.A., D.C. and G.L. wrote the paper.
This work was supported by a Fondo per gli Investimenti della Ricerca di Base (FIRB) program project [grant number RBAP11FRE9 to G.L.] from Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR) Italy.
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.183137.supplemental
- Received November 4, 2015.
- Accepted August 16, 2016.
- © 2016. Published by The Company of Biologists Ltd