title: The prion protein and neuronal zinc homeostasis.
abstract: Although the prion protein (PrP) is known to be the causative agent of the neurodegenerative transmissible spongiform encephalopathies, its normal cellular function remains elusive. Octapeptide repeats in the N terminus of PrP bind metal ions and are required for the endocytosis of PrP upon exposure of cells to copper or zinc. As the concentration of zinc in the extracellular spaces of the brain is higher than that for copper, we put forward the hypothesis that PrP is involved in neuronal zinc homeostasis; PrP might be involved in transport of zinc into the cell or might act as a zinc sensor. In prion disease, when the protein undergoes a conformational change to the infectious form, this function of PrP in zinc homeostasis might be compromised.
authors.affiliation: School of Biochemistry and Molecular Biology, University of Leeds, Leeds, UK LS2 9JT.
authors.forename: Nicole T
authors.initials: NT
authors.lastname: Watt
authors.forename: Nigel M
authors.initials: NM
authors.lastname: Hooper
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D003300:Copper / Q000737:chemistry; D004705:Endocytosis; D006801:Humans; D008670:Metals / Q000737:chemistry; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000378:metabolism*; D011328:Prions / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D015032:Zinc / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008670:Metals; D011328:Prions; D003300:Copper; D015032:Zinc