NR ASQW
AU Pimpinelli,F.; Lehmann,S.; Maridonneau-Parini,I.
TI The scrapie prion protein is present in flotillin-1-positive vesicles in central- but not peripheral-derived neuronal cell lines
QU European Journal of Neuroscience 2005 Apr; 21(8): 2063-72
PT journal article
AB Transmissible prion diseases are fatal neurodegenerative diseases associated with the conversion of the normal host prion protein (PrP c) into an abnormal isoform (PrPsc) that accumulates in brain. This pathology affects neurons of the central nervous system whereas no clear toxic effect has been reported for peripheral neurons. We examined the subcellular distribution of PrPc and PrPsc in the scrapie-infected mouse neuronal cell lines GT1-7 and N2a, derived, respectively, from the central and peripheral nervous system. We observed that in both cell types, PrPc is present in the endocytic compartment, mainly in LAMP-1-positive late endosomes, but excluded from LYAAT-1-lysosomes. In contrast, PrPsc was distributed differently in the two cell lines. In infected N2a, PrPsc and PrPc had comparable distribution patterns. In infected GT1-7, PrPsc is present in an additional vesicular compartment which is flotillin-1-positive. The level of expression of flotillin-1 is higher in GT1-7 than in N2a cells, but no difference is observed between infected and noninfected cells. In Alzheimer's disease patients, it has been reported that flotillin-1 is abundant in brain areas containing the beta-amyloid protein, which accumulates in endosomal vesicles in primary neurons. We propose that the flotillin compartment could store aggregated proteins and play a role in these neurodegenerative pathologies.
MH Amino Acid Transport Systems/metabolism; Animals; Antigens, CD/metabolism; Blotting, Western/methods; Cell Line; Central Nervous System/*cytology; Comparative Study; Endocytosis/physiology; Endopeptidases/secretion; Endosomes/metabolism; Extracellular Space/metabolism; Fluorescent Antibody Technique/methods; Lysosomes/secretion; Membrane Proteins/*metabolism; Mice; Neurons/cytology/*metabolism; Peripheral Nervous System/*cytology; PrPc Proteins/metabolism; PrPsc Proteins/*metabolism; Research Support, Non-U.S. Gov't; Time Factors; Transfection; beta-N-Acetylhexosaminidase/secretion
AD Institut de Pharmacologie et Biologie Structurale, Unite Mixte de Recherche 5089-Centre National de la Recherche Scientifique et Universite Paul Sabatier, 205 route de Narbonne, 31077 Toulouse, France.
SP englisch
PO Frankreich