NR ABMR
AU Borchelt,D.R.; Taraboulos,A.; Prusiner,S.B.
TI Evidence for synthesis of scrapie prion proteins in the endocytic pathway
QU The Journal of Biological Chemistry 1992 Aug 15; 267(23): 16188-99
PT journal article
AB Infectious scrapie prions are composed largely, if not entirely, of an abnormal isoform of the prion protein (PrP) which is designated PrPsc. A chromosomal gene encodes both the cellular prion protein (PrPc) as well as PrPsc. Pulse-chase experiments with scrapie-infected cultured cells indicate that PrPsc is formed by a post-translational process. PrP is translated in the endoplasmic reticulum, modified as it passes through the Golgi, and is transported to the cell surface. Release of nascent PrP from the cell surface by phosphatidylinositol-specific phospholipase C or hydrolysis with dispase prevented PrPsc synthesis. At 18 degrees C, the synthesis of PrPsc was inhibited under conditions that other investigators report a blockage of endosomal fusion with lysosomes. Our results suggest that PrPsc synthesis occurs after PrP transits from the cell surface. Whether all of the PrP molecules have an equal likelihood to be converted into PrPsc or only a distinct subset is eligible for conversion remains to be established. Identifying the subcellular compartment(s) of PrPsc synthesis should be of considerable importance in defining the molecular changes that distinguish PrPsc from PrPc.
IN Durch Freisetzung der normalen zellulären Prionproteine von der Zellmembran mit der phosphatidylinositolspezifischen Phospholipase C kann verhindert werden, dass Prionproteine in die scrapie-assoziierte Form umgewandelt werden.
MH Animals; Autoradiography; Cell Line; Electrophoresis, Polyacrylamide Gel; *Endocytosis; Kinetics; Methionine/metabolism; Molecular Weight; PrPsc Proteins; Prions/*biosynthesis/isolation & purification/metabolism; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Sulfur Radioisotopes; Temperature
AD Department of Neurology, University of California, San Francisco 94143.
SP englisch
PO USA