title: Subcellular distribution of the prion protein in sickness and in health.
abstract: The cellular prion protein (PrP(C)) is an ubiquitously expressed glycoprotein that is most abundant in the central nervous system. It is thought to play a role in many cellular processes, including neuroprotection, but may also contribute to Alzheimer's disease and some cancers. However, it is best known for its central role in the prion diseases, such as Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy (BSE), and scrapie. These protein misfolding diseases can be sporadic, acquired, or genetic and are caused by refolding of endogenous PrP(C) into a beta sheet-rich, pathogenic form, PrP(Sc). Once prions are present in the central nervous system, they increase and spread during a long incubation period that is followed by a relatively short clinical disease phase, ending in death. PrP molecules can be broadly categorized as either 'good' (cellular) PrP(C) or 'bad' (scrapie prion-type) PrP(Sc), but both populations are heterogeneous and different forms of PrP(C) may influence various cellular activities. Both PrP(C) and PrP(Sc) are localized predominantly at the cell surface, with the C-terminus attached to the plasma membrane via a glycosyl-phosphatidylinositol (GPI) anchor and both can exist in cleaved forms. PrP(C) also has cytosolic and transmembrane forms, and PrP(Sc) is known to exist in a variety of conformations and aggregation states. Here, we discuss the roles of different PrP isoforms in sickness and in health, and show the subcellular distributions of several forms of PrP that are particularly relevant for PrP(C) to PrP(Sc) conversion and prion-induced pathology in the hippocampus.
authors: Department of Cell Biology II, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands. Electronic address: s.godsave@outlook.com.
authors: Susan F
authors: SF
authors: Godsave
authors: Department of Cell Biology II, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands; Institute of Nanoscopy, University of Maastricht, Universiteitssingel 50, 6229 ER Maastricht, Netherlands(1).
authors: Peter J
authors: PJ
authors: Peters
authors: Department of Biochemistry and Centre for Prions and Protein Folding Diseases, University of Alberta, 204 Brain and Aging Research Building, Edmonton, Alberta T6G 2M8, Canada. Electronic address: wille@ualberta.ca.
authors: Holger
authors: H
authors: Wille
mesh_terms: D000818:Animals; D006801:Humans; D042541:Intracellular Space / Q000235:genetics / Q000378:metabolism*; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D018621:PrPC Proteins; D018620:PrPSc Proteins
keywords: Alzheimer's disease; Cancer; Neurodegeneration; Neuroprotection; PrP(C); PrP(Sc); Prion; Protein misfolding