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The abnormal isoform of the prion protein accumulates in late‐endosome‐like organelles in scrapie‐infected mouse brain
Author(s) -
Arnold Jane E.,
Tipler Carron,
Laszlo Lajos,
Hope James,
Landon Michael,
Mayer R. John
Publication year - 1995
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1711760412
Subject(s) - scrapie , gene isoform , endosome , organelle , prion protein , biology , virology , microbiology and biotechnology , neuroscience , pathology , medicine , genetics , disease , gene , intracellular
The prion encephalopathies are characterized by accumulation in the brain of the abnormal form PrP sc of a normal host gene product PrP c . The mechanism and site of formation of PrP sc from PrP c 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 PrP sc 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 PrP c will enter such compartments for normal degradation and the organelles may therfore act as chambers for the conversion of PrP c into infectious PrP sc in this murine model of scrapie.