Rapid cell-surface prion protein conversion revealed using a novel cell system

R Goold, S Rabbanian, L Sutton, R Andre, P Arora, J Moonga, AR Clarke, G Schiavo, P Jat, J Collinge, SJ Tabrizi

Research output: Contribution to journalArticle (Academic Journal)peer-review

102 Citations (Scopus)

Abstract

Prion diseases are fatal neurodegenerative disorders with unique transmissible properties. The infectious and pathological agent is thought to be a misfolded conformer of the prion protein. Little is known about the initial events in prion infection because the infecting prion source has been immunologically indistinguishable from normal cellular prion protein (PrPC). Here we develop a unique cell system in which epitope-tagged PrPC is expressed in a PrP knockdown (KD) neuroblastoma cell line. The tagged PrPC, when expressed in our PrP-KD cells, supports prion replication with the production of bona fide epitope-tagged infectious misfolded PrP (PrPSc). Using this epitope-tagged PrPSc, we study the earliest events in cellular prion infection and PrP misfolding. We show that prion infection of cells is extremely rapid occurring within 1 min of prion exposure, and we demonstrate that the plasma membrane is the primary site of prion conversion.
Translated title of the contributionRapid cell-surface prion protein conversion revealed using a novel cell system
Original languageEnglish
Pages (from-to)1 - 11
Number of pages11
JournalNature Communications
Volume2(281)
DOIs
Publication statusPublished - Apr 2011

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