| First Author | Rouvinski A | Year | 2014 |
| Journal | J Cell Biol | Volume | 204 |
| Issue | 3 | Pages | 423-41 |
| PubMed ID | 24493590 | Mgi Jnum | J:208258 |
| Mgi Id | MGI:5562578 | Doi | 10.1083/jcb.201308028 |
| Citation | Rouvinski A, et al. (2014) Live imaging of prions reveals nascent PrPSc in cell-surface, raft-associated amyloid strings and webs. J Cell Biol 204(3):423-41 |
| abstractText | Mammalian prions refold host glycosylphosphatidylinositol-anchored PrP(C) into beta-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 webs, sheltered from endocytosis. Prion strings observed by light and scanning electron microscopy were thin, micrometer-long 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 membrane-anchored PrP(Sc) amyloids. |
