Role of Prion protein-EGFR multimolecular complex during neuronal differentiation of human dental pulp-derived stem cells. Issue 2 (4th March 2018)

• Record Type: Journal Article
• Authors: Martellucci, Stefano; Manganelli, Valeria; Santacroce, Costantino; Santilli, Francesca; Piccoli, Luca; Sorice, Maurizio; Mattei, Vincenzo
• Is Part Of: Prion. Volume 12:Issue 2(2018)
• Page Start: 117
• Page End: 126
• Publication Date: 2018-03-04
• Subjects: dental pulp-derived stem cells -- EGF Receptor -- mesenchymal stem cells -- prion protein -- prions -- rafts; Protein folding -- Periodicals; Prions -- Periodicals; Proteins -- Biotechnology -- Periodicals; 572.633
• DOI: 10.1080/19336896.2018.1463797
• Languages: English
• ISSNs: 1933-6896

Abstract

ABSTRACT: Cellular prion protein (PrP C ) is expressed in a wide variety of stem cells in which regulates their self-renewal as well as differentiation potential. In this study we investigated the presence of PrP C in human dental pulp-derived stem cells (hDPSCs) and its role in neuronal differentiation process. We show that hDPSCs expresses early PrP C at low concentration and its expression increases after two weeks of treatment with EGF/bFGF. Then, we analyzed the association of PrP C with gangliosides and EGF receptor (EGF-R) during neuronal differentiation process. PrP C associates constitutively with GM2 in control hDPSCs and with GD3 only after neuronal differentiation. Otherwise, EGF-R associates weakly in control hDPSCs and more markedly after neuronal differentiation. To analyze the functional role of PrP C in the signal pathway mediated by EGF/EGF-R, a siRNA PrP was applied to ablate PrP C and its function. The treatment with siRNA PrP significantly prevented Akt and ERK1/2 phosphorylation induced by EGF. Moreover, siRNA PrP treatment significantly prevented neuronal-specific antigens expression induced by EGF/bFGF, indicating that cellular prion protein is essential for EGF/bFGF-induced hDPSCs differentiation. These results suggest that PrP C interact with EGF-R within lipid rafts, playing a role in the multimolecular signaling complexes involved in hDPSCs neuronal differentiation.