Methods for studying prion protein (PrP) metabolism and the formation of protease-resistant PrP in cell culture and cell-free systems. An update.
Transmissible spongiform encephalopathies (TSE) or prion diseases result in aberrant metabolism of prion protein (PrP) and the accumulation of a protease-resistant, insoluble, and possibly infectious form of PrP, PrP-res. Studies of PrP biosynthesis, intracellular trafficking, and degradation has been studied in a variety of tissue culture cells. Pulse-chase metabolic labeling studies in scrapie-infected cells indicated that PrP-res is made posttranslationally from an apparently normal protease-sensitive precursor, PrP-sen, after the latter reaches the cell surface. Cell-free reactions have provided evidence that PrP-res itself can induce the conversion of PrP-sen to PrP-res in a highly species- and strain-specific manner. These studies have shed light on the mechanism of PrP-res formation and suggest molecular bases for TSE species barrier effects and agent strain propagation.
NIH Rocky Mountain Laboratories, Hamilton, MT 59840, USA. byron_caughey@nih.gov
B
B
Caughey
G J
GJ
Raymond
S A
SA
Priola
D A
DA
Kocisko
R E
RE
Race
R A
RA
Bessen
P T
PT
Lansbury
B
B
Chesebro
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002474:Cell-Free System; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D008722:Methods; D011328:Prions / Q000032:analysis* / Q000378:metabolism
D011328:Prions; D010450:Endopeptidases