Insights into the physiological function of cellular prion protein

Abstract

Prions have been extensively studied since they represent a new class of infectious agents in which a protein, PrPsc (prion scrapie), appears to be the sole component of the infectious particle. They are responsible for transmissible spongiform encephalopathies, which affect both humans and animals. The mechanism of disease propagation is well understood and involves the interaction of PrPsc with its cellular isoform (PrPc) and subsequently abnormal structural conversion of the latter. PrPc is a glycoprotein anchored on the cell surface by a glycosylphosphatidylinositol moiety and expressed in most cell types but mainly in neurons. Prion diseases have been associated with the accumulation of the abnormally folded protein and its neurotoxic effects; however, it is not known if PrPc loss of function is an important component. New efforts are addressing this question and trying to characterize the physiological function of PrPc. At least four different mouse strains in which the PrP gene was ablated were generated and the results regarding their phenotype are controversial. Localization of PrPc on the cell membrane makes it a potential candidate for a ligand uptake, cell adhesion and recognition molecule or a membrane signaling molecule. Recent data have shown a potential role for PrPc in the metabolism of copper and moreover that this metal stimulates PrPc endocytosis. Our group has recently demonstrated that PrPc is a high affinity laminin ligand and that this interaction mediates neuronal cell adhesion and neurite extension and maintenance. Moreover, PrPc-caveolin-1 dependent coupling seems to trigger the tyrosine kinase Fyn activation. These data provide the first evidence for PrPc involvement in signal transduction.

Neurotrophin p75 Receptor Is Involved in Neuronal Damage by Prion Peptide-(106–126)

“…These problems include the types of interaction such as the type of interaction of the prion peptide with the extracellular region of p75 NTR , the signaling function of the different domains of the intracellular region, the identification of the events occurring down-stream the intracellular region (24,25), and the comparison of the role of p75 NTR with that of other cell surface proteins recently found to interact with prion peptide as the receptor for advanced glycation end-products (RAGE) (26), a 66-kDa protein with unknown function (27,28) a 37-kDa laminin receptor precursor (29), the formyl peptide receptor-like 1 (30), and the PrP C itself (9 …”

Revisiting Crick?s Dogma and the Impossibility of Reverse Translation

“…AAD46098). The normal form, called cellular PrP (PrPC), has a novel physiological function [42]. It can be converted into a modified protein (PrPSc) through a post-translational process.…”

Neuroimmune connections in ovine pharyngeal tonsil: potential site for prion neuroinvasion

“…Under physiological conditions, PrPc might notably play a role in neuronal and axonal development and in neurotogenesis through its interaction with laminin, a glycoprotein of the extracellular matrix, being involved in cell adhesion and proliferation (Cazaubon et al 2007;Martins et al 2001).…”