title: Cytosolic prion protein in neurons.
abstract: Localizing the cellular prion protein (PrPC) in the brain is necessary for understanding the pathogenesis of prion diseases. However, the precise ultrastructural localization of PrPC still remains enigmatic. We performed the first quantitative study of the ultrastructural localization of PrPC in the mouse hippocampus using high-resolution cryoimmunogold electron microscopy. PrPC follows the standard biosynthetic trafficking pathway with a preferential localization in late endosomal compartments and on the plasma membrane of neurons and neuronal processes. PrPC is found with the same frequency within the synaptic specialization and perisynaptically, but is almost completely excluded from synaptic vesicles. Unexpectedly, PrP is also found in the cytosol in subpopulations of neurons in the hippocampus, neocortex, and thalamus but not the cerebellum. Cytosolic PrP may have altered susceptibility to aggregation, suggesting that these neurons might play a significant role in the pathogenesis of prion diseases, in particular those mammals harboring mutant PrP genes.
authors.affiliation: The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Mironov
authors.forename: Diane
authors.initials: D
authors.lastname: Latawiec
authors.forename: Holger
authors.initials: H
authors.lastname: Wille
authors.forename: Essia
authors.initials: E
authors.lastname: Bouzamondo-Bernstein
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Legname
authors.forename: R Anthony
authors.initials: RA
authors.lastname: Williamson
authors.forename: Dennis
authors.initials: D
authors.lastname: Burton
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: DeArmond
authors.forename: Stanley B
authors.initials: SB
authors.lastname: Prusiner
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Peters
mesh_terms: D000818:Animals; D000918:Antibody Specificity; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism* / Q000648:ultrastructure; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D019581:Neuropil / Q000378:metabolism / Q000648:ultrastructure; D015388:Organelles / Q000378:metabolism / Q000648:ultrastructure; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000648:ultrastructure
chemical_list: D018621:PrPC Proteins