NR AHEG
AU Lehmann,S.; Harris,D.A.
TI Mutant and infectious prion proteins display common biochemical properties in cultured cells
QU The Journal of Biological Chemistry 1996 Jan 19; 271(3): 1633-7
ER J Biol Chem 2000 Jan 14;275(2):1520
PT journal article
AB Prion diseases are unusual neurodegenerative disorders that can be both infectious and inherited. Both forms are hypothesized to result from a posttranslational structural alteration in the cell surface glycoprotein PrPc (cellular isoform of the prion protein) that converts it into the protease-resistant isoform PrPsc (scrapie isoform of the prion protein). However, a direct comparison of molecular events underlying these two manifestations of prion diseases has not been possible, because there has been no cell culture model for the familial forms. We report here that when mutant prion proteins associated with three different inherited prion disorders of humans are expressed as their murine homologues in cultured Chinese hamster ovary cells, the proteins are protease-resistant and detergent-insoluble, two biochemical properties characteristic of infectious PrPsc. In addition, each mutant protein remains tightly associated with the plasma membrane after enzymatic cleavage of its glycosylphosphatidylinositol anchor, a property that we now show is also typical of infectious PrPsc. The cell culture system described here is the first in vitro model for familial prion diseases and provides compelling evidence that infectious and genetic cases share common molecular features.
ZR 49
MH Amino Acid Sequence; Animal; CHO Cells; Cell Line; Cell Membrane/metabolism; Detergents; Endopeptidases/metabolism; Hamsters; Human; Mice; Neuroblastoma; Phenotype; Phospholipase C/metabolism; *Point Mutation; PrPsc Proteins/biosynthesis/isolation & purification/metabolism; Prions/biosynthesis/isolation & purification/*metabolism; Recombinant Proteins/biosynthesis/metabolism; Solubility; Support, Non-U.S. Gov't; Transfection; Tumor Cells, Cultured
AD Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA
SP englisch
PO USA
OR Prion-Krankheiten L