title: Characterization of prion protein function by focal neurite stimulation.
abstract: 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 PrPCmight promote neurite outgrowth and facilitate growth cone guidance.
authors: Department of Neuroscience, Laboratory of Prion Biology, Scuola Internazionale Superiore di Studi Avanzati (SISSA), I-34136 Trieste, Italy.
authors: Ladan
authors: 0000-0001-6388-8869
authors: L
authors: Amin
authors: Department of Neuroscience, Laboratory of Prion Biology, Scuola Internazionale Superiore di Studi Avanzati (SISSA), I-34136 Trieste, Italy.
authors: Xuan T A
authors: XT
authors: Nguyen
authors: Department of Neuroscience, Laboratory of Prion Biology, Scuola Internazionale Superiore di Studi Avanzati (SISSA), I-34136 Trieste, Italy.
authors: Irene Giulia
authors: IG
authors: Rolle
authors: Max Planck Institute for Biophysical Chemistry, D-37077 Göttingen, Germany.
authors: Elisa
authors: E
authors: D'Este
authors: Department of Neuroscience, Laboratory of Prion Biology, Scuola Internazionale Superiore di Studi Avanzati (SISSA), I-34136 Trieste, Italy.
authors: Gabriele
authors: G
authors: Giachin
authors: Department of Neuroscience, Laboratory of Prion Biology, Scuola Internazionale Superiore di Studi Avanzati (SISSA), I-34136 Trieste, Italy.
authors: Thanh Hoa
authors: TH
authors: Tran
authors: Department for Production of Diagnostic Reagents and Research, Blood Transfusion Centre of Slovenia, 1000 Ljubljana, Slovenia.
authors: Vladka Čurin
authors: VČ
authors: Šerbec
authors: Optical Manipulation (OM)-Lab, Institute of Materials (IOM), National Research Council (CNR), I-34149 Trieste, Italy cojoc@iom.cnr.it legname@sissa.it.
authors: Dan
authors: 0000-0003-2243-4478
authors: D
authors: Cojoc
authors: Department of Neuroscience, Laboratory of Prion Biology, Scuola Internazionale Superiore di Studi Avanzati (SISSA), I-34136 Trieste, Italy cojoc@iom.cnr.it legname@sissa.it.
authors: Giuseppe
authors: G
authors: Legname
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D000072002:Prion Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D019006:Neural Cell Adhesion Molecules; D000072002:Prion Proteins; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins
keywords: Growth cone guidance and signaling; Local delivery; Neurite outgrowth; Prion protein