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

被引：111
作者：
Goold, R. [1 ]
Rabbanian, S. [1 ]
Sutton, L. [1 ]
Andre, R. [1 ]
Arora, P. [2 ]
Moonga, J. [1 ]
Clarke, A. R. [2 ]
Schiavo, G. [3 ]
Jat, P. [1 ]
Collinge, J. [1 ,2 ]
Tabrizi, S. J. [1 ]
机构：
[1] UCL, Inst Neurol, Dept Neurodegenerat Dis, London WC1N 3BG, England
[2] UCL, Inst Neurol, MRC Prion Unit, London WC1N 3BG, England
[3] Canc Res UK London Res Inst, Mol NeuroPathobiol Grp, London WC2A 3LY, England
来源：
NATURE COMMUNICATIONS | 2011年 / 2卷
基金：
英国医学研究理事会;
关键词：
LOW-DENSITY-LIPOPROTEIN; SCRAPIE; ACCUMULATION; PRP; INFECTIVITY; RESISTANT; MICE; CHOLESTEROL; ENDOCYTOSIS; COMPONENTS;
D O I：
10.1038/ncomms1282
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
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页数：11
相关论文
共 54 条
  • [1] Cellular factors implicated in prion replication
    Abid, Karim
    Morales, Rodrigo
    Soto, Claudio
    [J]. FEBS LETTERS, 2010, 584 (11) : 2409 - 2414
  • [2] Mouse neuroblastoma cells release prion infectivity associated with exosomal vesicles
    Alais, Sandrine
    Simoes, Sabrina
    Baas, Dominique
    Lehmann, Sylvain
    Raposo, Graca
    Darlix, Jean Luc
    Leblanc, Pascal
    [J]. BIOLOGY OF THE CELL, 2008, 100 (10) : 603 - 615
  • [3] THE ABNORMAL ISOFORM OF THE PRION PROTEIN ACCUMULATES IN LATE-ENDOSOME-LIKE ORGANELLES IN SCRAPIE-INFECTED MOUSE-BRAIN
    ARNOLD, JE
    TIPLER, C
    LASZLO, L
    HOPE, J
    LANDON, M
    MAYER, RJ
    [J]. JOURNAL OF PATHOLOGY, 1995, 176 (04) : 403 - 411
  • [4] Visualization of prion infection in transgenic mice expressing green fluorescent protein-tagged prion protein
    Barmada, SJ
    Harris, DA
    [J]. JOURNAL OF NEUROSCIENCE, 2005, 25 (24) : 5824 - 5832
  • [5] Stimulation of PrPC retrograde transport toward the endoplasmic reticulum increases accumulation of PrPSc in prion-infected cells
    Béranger, F
    Mangé, A
    Goud, B
    Lehmann, S
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (41) : 38972 - 38977
  • [6] A large-scale RNAi screen in human cells identifies new components of the p53 pathway
    Berns, K
    Hijmans, EM
    Mullenders, J
    Brummelkamp, TR
    Velds, A
    Heimerikx, M
    Kerkhoven, RM
    Madiredjo, M
    Nijkamp, W
    Weigelt, B
    Agami, R
    Ge, W
    Cavet, G
    Linsley, PS
    Beijersbergen, RL
    Bernards, R
    [J]. NATURE, 2004, 428 (6981) : 431 - 437
  • [7] BORCHELT DR, 1992, J BIOL CHEM, V267, P16188
  • [8] Cultured cell sublines highly susceptible to prion infection
    Bosque, PJ
    Prusiner, SB
    [J]. JOURNAL OF VIROLOGY, 2000, 74 (09) : 4377 - 4386
  • [9] SCRAPIE-INFECTED MURINE NEURO-BLASTOMA CELLS PRODUCE PROTEASE-RESISTANT PRION PROTEINS
    BUTLER, DA
    SCOTT, MRD
    BOCKMAN, JM
    BORCHELT, DR
    TARABOULOS, A
    HSIAO, KK
    KINGSBURY, DT
    PRUSINER, SB
    [J]. JOURNAL OF VIROLOGY, 1988, 62 (05) : 1558 - 1564
  • [10] CAUGHEY B, 1991, J BIOL CHEM, V266, P18217
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