Characterization of prion protein function by focal neurite stimulation

Abstract

The cellular prion protein (PrPC) 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 (GC). Local stimulation of wild-type GC with full-length recPrP induced neurite outgrowth and rapid GC turning towards the source. This effect is shown to be concentration dependent. Notably, PrPC knockout GC were insensitive to recPrP stimulation but this property was rescued in PrP knockout GC expressing GFP-PrP. Altogether, our findings indicate that recPrP functions as a signaling molecule and its homophilic interaction with membrane-anchored PrPC may promote neurite outgrowth and facilitate GC guidance.