AUTHOR=Roucou Xavier 

TITLE=Regulation of PrPC signaling and processing by dimerization

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=2

YEAR=2014

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2014.00057

DOI=10.3389/fcell.2014.00057

ISSN=2296-634X

ABSTRACT=<p>The cellular prion protein (PrP<sup>C</sup>) is a glycosylphosphatidylinositol (GPI)-anchored protein present at the cell surface. PrP<sup>C</sup> 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<sup>C</sup>-activated signaling pathways. Remarkably, PrP<sup>C</sup> may be inactivated either by physiological endoproteolysis and release of the N-terminal domain, or by ectodomain shedding. Ligand-induced PrP<sup>C</sup> dimerization or enforced dimerization of PrP<sup>C</sup> indicate that PrP<sup>C</sup> dimerization represents an important molecular switch for both intracellular signaling and inactivation by the release of PrP<sup>C</sup> N-terminal domain or shedding. In this review, we summarize evidence that cell surface receptor activity of PrP<sup>C</sup> is finely regulated by dimerization.</p>