NR ABGG
AU Beranger,F.; Mange,A.; Goud,B.; Lehmann,S.
TI Stimulation of PrPc retrograde transport toward the endoplasmic reticulum increases accumulation of PrPsc in prion-infected cells
QU The Journal of Biological Chemistry 2002 Oct 11; 277(41): 38972-7
IA http://www.jbc.org/cgi/content/full/277/41/38972
PT journal article
AB Prion diseases are fatal and transmissible neurodegenerative disorders characterized by the accumulation of an abnormally folded isoform of the cellular prion protein (PrPc) denoted PrPsc. To identify intracellular organelles involved in PrPsc formation, we studied the role of the Ras-related GTP-binding proteins Rab4 and Rab6a in intracellular trafficking of the prion protein and production of PrPsc. When a dominant-negative Rab4 mutant or a constitutively active GTP-bound Rab6a protein was overexpressed in prion-infected neuroblastoma N2a cells, there was a marked increase of PrPsc formation. By immunofluorescence and cell fractionation studies, we have shown that expression of Rab6a-GTP delocalizes PrP within intracellular compartments, leading to an accumulation in the endoplasmic reticulum. These results suggest that prion protein can be subjected to retrograde transport toward the endoplasmic reticulum and that this compartment may play a significant role in PrPsc conversion.
MH Animals; Biological Transport/*physiology; Cell Fractionation; Endoplasmic Reticulum/*metabolism; Guanosine Triphosphate/metabolism; Mice; Mutation; Neuroblastoma; PrPc Proteins/genetics/*metabolism; Proto-Oncogene Proteins c-myc/genetics/metabolism; Research Support, Non-U.S. Gov't; Tumor Cells, Cultured; rab GTP-Binding Proteins/genetics/*metabolism; rab4 GTP-Binding Proteins/genetics/*metabolism
AD Institut de Genetique Humaine, UPR CNRS1142, 141 Rue de la Cardonille, 34396, Montpellier Cedex 5, France. Florence.Beranger@igh.cnrs.fr
SP englisch
PO USA