The abnormal isoform of the prion protein accumulates in late‐endosome‐like organelles in scrapie‐infected mouse brain

Jane E. Arnold, Carron Tipler, Lajos Laszlo, James Hope, Michael Landon, R. John Mayer

Research output: Article

142 Citations (Scopus)

Abstract

The prion encephalopathies are characterized by accumulation in the brain of the abnormal form PrPsc of a normal host gene product PrPc. The mechanism and site of formation of PrPsc from PrPc are currently unknown. In this study, ME7 scrapie‐infected mouse brain was used to show, both biochemically and by double‐labelled immunogold electron microscopy, that proteinase K‐resistant PrPsc is enriched in subcellular structures which contain the cation‐independent mannose 6‐phosphate receptor, ubiquitin‐protein conjugates, β‐glucuronidase, and cathepsin B, termed late endosome‐like organelles. The glycosylinositol phospholipid membrane‐anchored PrPc will enter such compartments for normal degradation and the organelles may therfore act as chambers for the conversion of PrPc into infectious PrPsc in this murine model of scrapie.

Original languageEnglish
Pages (from-to)403-411
Number of pages9
JournalThe Journal of Pathology
Volume176
Issue number4
DOIs
Publication statusPublished - aug. 1995

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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