Alternative fates of newly formed PrP upon prion conversion on the plasma membrane
نویسندگان
چکیده
Rob Goold, Chris McKinnon, Samira Rabbanian, John Collinge, Giampietro Schiavo and Sarah J. Tabrizi* Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK MRC Prion Unit, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK Molecular Neuropathobiology Laboratory, London Research Institute, Cancer Research UK, Lincoln’s Inn Fields, London WC2A 3LY, UK
منابع مشابه
Alternative fates of newly formed PrPSc upon prion conversion on the plasma membrane.
Prion diseases are fatal neurodegenerative diseases characterised by the accumulation of misfolded prion protein (PrP(Sc)) in the brain. They are caused by the templated misfolding of normal cellular protein, PrP(C), by PrP(Sc). We have recently generated a unique cell system in which epitope-tagged PrP(C) competent to produce bona fide PrP(Sc) is expressed in neuroblastoma cells. Using this sy...
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The molecular basis of the prion model and the mechanistic models of the prion amplification are summarized. The infection is a conversion of the host encoded prion protein PrP from its cellular isoform PrPC into a pathological and infectious isoform PrPSc. The conversion process was investigated by in vitro studies on recombinant PrP. Dimeric and oligomeric PrP conformations were identified as...
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A direct physical interaction of the prion protein isoforms is a key element in prion conversion. Which sites interact first and which parts of PrP(c) are converted subsequently is presently not known in detail. We hypothesized that structural changes induced by PrP(Sc) interaction occur in more than one interface and subsequently propagate within the PrP(C) substrate, like epicenters of struct...
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To clarify the cellular mechanisms for the establishment of prion infection, we analyzed the intracellular dynamics of inoculated and newly generated abnormal isoform of prion protein (PrP(Sc)) in Neuro2a cells. Within 24h after inoculation, the newly generated PrP(Sc) was evident at the plasma membrane, in early endosomes, and in late endosomes, but this PrP(Sc) was barely evident in lysosomes...
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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...
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