Prion Protein in Stem Cells: A Lipid Raft Component Involved in the Cellular Differentiation Process.

Stefano Martellucci,Valeria Manganelli,Costantino Santacroce,Vincenzo Mattei,Francesca Santilli,Maurizio Sorice

doi:10.3390/ijms21114168

Stefano Martellucci, Valeria Manganelli + Show 4 more

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https://doi.org/10.3390/ijms21114168

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Abstract

The prion protein (PrP) is an enigmatic molecule with a pleiotropic effect on different cell types; it is localized stably in lipid raft microdomains and it is able to recruit downstream signal transduction pathways by its interaction with various biochemical partners. Since its discovery, this lipid raft component has been involved in several functions, although most of the publications focused on the pathological role of the protein. Recent studies report a key role of cellular prion protein (PrPC) in physiological processes, including cellular differentiation. Indeed, the PrPC, whose expression is modulated according to the cell differentiation degree, appears to be part of the multimolecular signaling pathways of the neuronal differentiation process. In this review, we aim to summarize the main findings that report the link between PrPC and stem cells.

Highlights

IntroductionThe prion protein (PrP), a molecule discovered by Stanley Prusiner, is involved in the transmissible spongiform encephalopathies (TSEs), such as family fatal insomnia (FFI), Creutzfeldt–Jakob disease (CJD), Gerstmann–Sträussler–Scheinker (GSS), and other pathologies [1,2]
The prion protein (PrP), a molecule discovered by Stanley Prusiner, is involved in the transmissible spongiform encephalopathies (TSEs), such as family fatal insomnia (FFI), Creutzfeldt–Jakob disease (CJD), Gerstmann–Sträussler–Scheinker (GSS), and other pathologies [1,2].Many studies have shown that two possible protein tridimensional conformations may exist: the cellular prion protein (PrPC), normally expressed in all nucleated cells; and the scrapie prion protein (PrPSc), which is involved in the TSEs
A recent study published by Martellucci et al has furnished evidence of the presence of PrPC in human dental pulp-derived stem cells and of its role in the neuronal differentiation process; in addition, it has been shown that the lipid raft’s integrity is essential for the PrPC-induced signal pathways, and that is essential for the neuronal differentiation process of hDPSCs induced by the epidermal growth factor and basic fibroblast growth factor (EGF/bFGF) [42,43]

Summary

Introduction

The prion protein (PrP), a molecule discovered by Stanley Prusiner, is involved in the transmissible spongiform encephalopathies (TSEs), such as family fatal insomnia (FFI), Creutzfeldt–Jakob disease (CJD), Gerstmann–Sträussler–Scheinker (GSS), and other pathologies [1,2]. A recent study published by Martellucci et al has furnished evidence of the presence of PrPC in human dental pulp-derived stem cells (hDPSCs) and of its role in the neuronal differentiation process; in addition, it has been shown that the lipid raft’s integrity is essential for the PrPC-induced signal pathways, and that is essential for the neuronal differentiation process of hDPSCs induced by the epidermal growth factor and basic fibroblast growth factor (EGF/bFGF) [42,43]. PrPC is constitutively present in lipid rafts [45] and in a wide variety of stem cells [39,40]; it is involved in stemness modulation and, mostly, in the self-renewal and proliferation of tissue-resident stem cells and the neuronal differentiation of neural stem cells [46]. The purpose of this review is to highlight the role of PrPC as a lipid raft component during neuronal and neuronal differentiation processes

Prion Protein as Raft Component

Prion Protein and Stem Cells

Prion Protein in Neural and Neuronal Differentiation Processes

Findings

Conclusions