NR AKXF
AU Singh,N.; Zanusso,G.; Chen,S.G.; Fujioka,H.; Richardson,S.; Gambetti,P.; Petersen,R.B.
TI Prion protein aggregation reverted by low temperature in transfected cells carrying a prion protein gene mutation
QU The Journal of Biological Chemistry 1997 Nov 7; 272(45): 28461-70
PT journal article
AB Prion diseases are characterized by the conversion of the normal cellular prion protein (PrPc), a glycoprotein that is anchored to the cell membrane by a glycosylphosphatidylinositol moiety, into an isoform that is protease-resistant (PrPres) and pathogenic. In inherited prion diseases, mutations in the prion protein (PrPm) engender the conversion of PrPm into PrPres. We developed a cell model of Gerstmann-Sträussler-Scheinker disease, a neurodegenerative condition characterized by PrPm-containing amyloid deposits and neuronal loss, by expressing the Gerstmann-Sträussler-Scheinker haplotype Q217R-129V in human neuroblastoma cells. By comparison to PrPc, this genotype results in the following alterations of PrPm: 1) expression of an aberrant form lacking the glycosylphosphatidylinositol anchor, 2) increased aggregation and protease resistance, and 3) impaired transport to the cell surface. Most of these alterations are temperature-sensitive, indicating that they are due to misfolding of PrPm.
MH Cell Membrane/metabolism; Cold; Genotype; Gerstmann-Sträussler-Scheinker Disease/genetics; Human; *Mutation; Phospholipase C/metabolism; Prions/chemistry/*genetics; Protein Folding; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Surface Properties; Transfection; Tumor Cells, Cultured
AD Division of Neuropathology, Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA
SP englisch
PO USA