期刊
JOURNAL OF CELL SCIENCE
卷 129, 期 20, 页码 3878-3891出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.183137
关键词
Prion protein; Neurite outgrowth; Growth cone guidance and signaling; Local delivery
类别
资金
- Fondo per gli Investimenti della Ricerca di Base (FIRB) program from Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR) Italy [RBAP11FRE9]
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.
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