Live imaging of prions reveals nascent PrPSc in cell-surface, raft-associated amyloid strings and webs.

ABSTRACT: Mammalian prions refold host glycosylphosphatidylinositol-anchored PrP(C) into β-sheet-rich PrP(Sc). PrP(Sc) is rapidly truncated into a C-terminal PrP27-30 core that is stable for days in endolysosomes. The nature of cell-associated prions, their attachment to membranes and rafts, and their subcellular locations are poorly understood; live prion visualization has not previously been achieved. A key obstacle has been the inaccessibility of PrP27-30 epitopes. We overcame this hurdle by focusing on nascent full-length PrP(Sc) rather than on its truncated PrP27-30 product. We show that N-terminal PrP(Sc) epitopes are exposed in their physiological context and visualize, for the first time, PrP(Sc) in living cells. PrP(Sc) resides for hours in unexpected cell-surface, slow moving strings and w

SUBMITTER: Rouvinski A 

PROVIDER: S-EPMC3912534 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature