ArticleThe Journal of biological chemistry2011
An N-terminal polybasic domain and cell surface localization are required for mutant prion protein toxicity.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed.
- Chemo-omic pipeline enables discovery of prion synaptotoxic pathways and inhibitory drugs.PLoS pathogens · 2026Article
- Prion Protein-Derived Cell-Penetrating Peptide Inhibits Type II Diabetes-Associated Islet Amyloid Polypeptide Aggregation and Cytotoxicity.Biochemistry · 2026Article
- Chemo-omic pipeline enables discovery of prion synaptotoxic pathways and inhibitory drugs.bioRxiv : the preprint server for biology · 2026Article
- Membrane-anchored PrPSc is the trigger for prion synaptotoxicity.PLoS pathogens · 2026Article
- Mutant prion protein enhances NMDA receptor activity, activates PKC, and triggers rapid excitotoxicity in mice.The Journal of clinical investigation · 2025Article
- Prion Protein Endoproteolysis: Cleavage Sites, Mechanisms and Connections to Prion Disease.Journal of neurochemistry · 2025Review
- Designed Cell-Penetrating Peptide Constructs for Inhibition of Pathogenic Protein Self-Assembly.Pharmaceutics · 2024Review
- Abnormal synaptic architecture in iPSC-derived neurons from a multi-generational family with genetic Creutzfeldt-Jakob disease.Stem cell reports · 2024Article
- Biological function of sialic acid and sialylation in human health and disease.Cell death discovery · 2024Review
- Review
- Evidence for preexisting prion substrain diversity in a biologically cloned prion strain.PLoS pathogens · 2023Article
- Mechanisms of prion-induced toxicity.Cell and tissue research · 2023Review
- Rapid ex vivo reverse genetics identifies the essential determinants of prion protein toxicity.Brain pathology (Zurich, Switzerland) · 2023Article
- Antibody binding modulates the dynamics of the membrane-bound prion protein.Biophysical journal · 2022Article
- N-Terminal Regions of Prion Protein: Functions and Roles in Prion Diseases.International journal of molecular sciences · 2020Review
- Transgenic Overexpression of the Disordered Prion Protein N1 Fragment in Mice Does Not Protect Against Neurodegenerative Diseases Due to Impaired ER Translocation.Molecular neurobiology · 2020Article
- Intrinsic toxicity of the cellular prion protein is regulated by its conserved central region.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Structural Features of Heparin and Its Interactions With Cellular Prion Protein Measured by Surface Plasmon Resonance.Frontiers in molecular biosciences · 2020Article
- Altered Domain Structure of the Prion Protein Caused by CuStructure (London, England : 1993) · 2019Article
- Prion neurotoxicity.Brain pathology (Zurich, Switzerland) · 2019Review
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Authors and funding
6 authors.
Funding
Abstract
There is evidence that alterations in the normal physiological activity of PrP(C) contribute to prion-induced neurotoxicity. This mechanism has been difficult to investigate, however, because the normal function of PrP(C) has remained obscure, and there are no assays available to measure it. We recently reported that cells expressing PrP deleted for residues 105-125 exhibit spontaneous ionic currents and hypersensitivity to certain classes of cationic drugs. Here, we utilize cell culture assays based on these two phenomena to test how changes in PrP sequence and/or cellular localization affect the functional activity of the protein. We report that the toxic activity of Δ105-125 PrP requires localization to the plasma membrane and depends on the presence of a polybasic amino acid segment at the N terminus of PrP. Several different deletions spanning the central region as well as three disease-associated point mutations also confer toxic activity on PrP. The sequence domains identified in our study are also critical for PrP(Sc) formation, suggesting that common structural features may govern both the functional activity of PrP(C) and its conversion to PrP(Sc).
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