NR AOLV
AU Mironov,A.Jr.; Latawiec,D.; Wille,H.; Bouzamondo-Bernstein,E.; Legname,G.; Williamson,R.A.; Burton,D.R.; DeArmond,S.J.; Prusiner,S.B.; Peters,P.J.
TI Cytosolic prion protein in neurons
QU Journal of Neuroscience 2003 Aug 6; 23(18): 7183-93
PT journal article
AB 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.
MH Animal; Antibody Specificity; Cell Membrane/metabolism/ultrastructure; Cytosol/*metabolism/ultrastructure; Dendrites/metabolism/ultrastructure; Endosomes/metabolism/ultrastructure; Fluorescent Antibody Technique; Hamsters; Hippocampus/metabolism/ultrastructure; Immunohistochemistry/methods; Mice; Mice, Inbred Strains; Mice, Transgenic; Neurons/*metabolism/ultrastructure; Neuropil/metabolism/ultrastructure; Organelles/metabolism/ultrastructure; PrPc Proteins/genetics/*metabolism; Synaptic Vesicles/ultrastructure
AD Alexander Mironov Jr, Peter J. Peters, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands; Diane Latawiec, Holger Wille, Essia Bouzamondo-Bernstein, Giuseppe Legname, Stephen J. DeArmond, Stanley B. Prusiner, Institute for Neurodegenerative Diseases, University of California, San Francisco, California 94143, USA; Holger Wille, Giuseppe Legname, Stanley B. Prusiner, Department of Neurology, University of California, San Francisco, California 94143, USA; Essia Bouzamondo-Bernstein, Stephen J. DeArmond, Department of Pathology, University of California, San Francisco, California 94143, USA; Stanley B. Prusiner, Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143, USA; R. Anthony Williamson, Dennis Burton, Scripps Research Institute, La Jolla, California 92037, USA
SP englisch
PO USA