PMID- 21505437
OWN - NLM
STAT- MEDLINE
DCOM- 20110816
LR  - 20211020
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 2
DP  - 2011
TI  - Rapid cell-surface prion protein conversion revealed using a novel cell system.
PG  - 281
LID - 10.1038/ncomms1282 [doi]
AB  - 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 (PrP(C)). Here we develop a 
      unique cell system in which epitope-tagged PrP(C) is expressed in a PrP knockdown 
      (KD) neuroblastoma cell line. The tagged PrP(C), when expressed in our PrP-KD 
      cells, supports prion replication with the production of bona fide epitope-tagged 
      infectious misfolded PrP (PrP(Sc)). Using this epitope-tagged PrP(Sc), 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.
FAU - Goold, R
AU  - Goold R
AD  - Department of Neurodegenerative Disease, Institute of Neurology, University 
      College London, Queen Square, London WC1N 3BG, UK.
FAU - Rabbanian, S
AU  - Rabbanian S
FAU - Sutton, L
AU  - Sutton L
FAU - Andre, R
AU  - Andre R
FAU - Arora, P
AU  - Arora P
FAU - Moonga, J
AU  - Moonga J
FAU - Clarke, A R
AU  - Clarke AR
FAU - Schiavo, G
AU  - Schiavo G
FAU - Jat, P
AU  - Jat P
FAU - Collinge, J
AU  - Collinge J
FAU - Tabrizi, S J
AU  - Tabrizi SJ
LA  - eng
GR  - G0700877/MRC_/Medical Research Council/United Kingdom
GR  - MC_U123160656/MRC_/Medical Research Council/United Kingdom
GR  - MC_U123192748/MRC_/Medical Research Council/United Kingdom
GR  - DH_/Department of Health/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Membrane Proteins)
RN  - 0 (Prions)
SB  - IM
CIN - Nat Rev Mol Cell Biol. 2011 May;12(5):278. PMID: 21508984
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Fluorescent Antibody Technique
MH  - Gene Knockdown Techniques
MH  - Membrane Proteins/*chemistry
MH  - Mice
MH  - Prion Diseases/*metabolism
MH  - Prions/*chemistry/genetics
MH  - *Protein Folding
MH  - Protein Transport
MH  - RNA Interference
MH  - Time Factors
PMC - PMC3104518
EDAT- 2011/04/21 06:00
MHDA- 2011/08/17 06:00
CRDT- 2011/04/21 06:00
PHST- 2010/10/08 00:00 [received]
PHST- 2011/03/17 00:00 [accepted]
PHST- 2011/04/21 06:00 [entrez]
PHST- 2011/04/21 06:00 [pubmed]
PHST- 2011/08/17 06:00 [medline]
AID - ncomms1282 [pii]
AID - 10.1038/ncomms1282 [doi]
PST - ppublish
SO  - Nat Commun. 2011;2:281. doi: 10.1038/ncomms1282.