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

Alexander Rouvinski, Sharon Karniely, Maria Kounin, Sanaa Moussa, Miri D. Goldberg, Gabriela Warburg, Roman Lyakhovetsky, Dulce Papy-Garcia, Janine Kutzsche, Carsten Korth, George A. Carlson, Susan F. Godsave, Peter J. Peters, Katarina Luhr, Krister Kristensson, Albert Taraboulos*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Mammalian prions refold host glycosylphosphatidylinositol- anchored PrPC into β-sheet- rich PrPSc. PrPSc 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 PrPSc rather than on its truncated PrP27-30 product. We show that N-terminal PrPSc epitopes are exposed in their physiological context and visualize, for the first time, PrPSc in living cells. PrPSc resides for hours in unexpected cell-surface, slow moving strings and webs, sheltered from endocytosis. Prion strings observed by light and scanning electron microscopy were thin, micrometerlong structures. They were firmly cell associated, resisted phosphatidylinositol-specific phospholipase C, aligned with raft markers, fluoresced with thioflavin, and were rapidly abolished by anti-prion glycans. Prion strings and webs are the first demonstration of membraneanchored PrPSc amyloids.

Original languageAmerican English
Pages (from-to)423-441
Number of pages19
JournalJournal of Cell Biology
Issue number3
StatePublished - 3 Feb 2014


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