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Front Cell Dev Biol. 2014 Oct 9;2:57. doi: 10.3389/fcell.2014.00057. eCollection 2014.

Regulation of PrP(C) signaling and processing by dimerization.

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1
Department of Biochemistry, Faculty of Medicine, Université de Sherbrooke Sherbrooke, QC, Canada.

Abstract

The cellular prion protein (PrP(C)) is a glycosylphosphatidylinositol (GPI)-anchored protein present at the cell surface. PrP(C) N-terminal moiety is intrinsically disordered and is able to interact with a variety of ligands. Physiological ligands have neurotrophic activity, whilst others, including protein toxic oligomers, have neurotoxic functions. These two opposite activities involve different interacting partners and result from different PrP(C)-activated signaling pathways. Remarkably, PrP(C) may be inactivated either by physiological endoproteolysis and release of the N-terminal domain, or by ectodomain shedding. Ligand-induced PrP(C) dimerization or enforced dimerization of PrP(C) indicate that PrP(C) dimerization represents an important molecular switch for both intracellular signaling and inactivation by the release of PrP(C) N-terminal domain or shedding. In this review, we summarize evidence that cell surface receptor activity of PrP(C) is finely regulated by dimerization.

KEYWORDS:

dimerization; neurodegeneration; neuroprotection; prion protein trafficking; signaling

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