ArticleThe Journal of biological chemistry2010
Endogenous proteolytic cleavage of disease-associated prion protein to produce C2 fragments is strongly cell- and tissue-dependent.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 68 citations in OpenAlex.
- Cellular prion protein and its derived peptides: multifaceted roles in neurodegenerative diseases and potential as biomarkers.Cell & bioscience · 2026Review
- Prion Protein Endoproteolysis: Cleavage Sites, Mechanisms and Connections to Prion Disease.Journal of neurochemistry · 2025Review
- Effect of host and strain factors on α-synuclein prion pathogenesis.Trends in neurosciences · 2024Review
- Application of N-Terminal Labeling Methods Provide Novel Insights into Endoproteolysis of the Prion ProteinACS chemical neuroscience · 2024Article
- Full-length prion protein incorporated into prion aggregates is a marker for prion strain-specific destabilization of aggregate structure following cellular uptake.Journal of biochemistry · 2023Article
- Beta-endoproteolysis of the cellular prion protein by dipeptidyl peptidase-4 and fibroblast activation protein.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- PrPFrontiers in molecular neuroscience · 2021Review
- A seven-residue deletion in PrP leads to generation of a spontaneous prion formed from C-terminal C1 fragment of PrP.The Journal of biological chemistry · 2020Article
- Host prion protein expression levels impact prion tropism for the spleen.PLoS pathogens · 2020Article
- Prion protein N1 cleavage peptides stimulate microglial interaction with surrounding cells.Scientific reports · 2020Article
- Review
- Independent amplification of co-infected long incubation period low conversion efficiency prion strains.PLoS pathogens · 2018Article
- Prion protein facilitates retinal iron uptake and is cleaved at the β-site: Implications for retinal iron homeostasis in prion disorders.Scientific reports · 2017Article
- Divergent prion strain evolution driven by PrPNature communications · 2017Article
- Comparison of abnormal isoform of prion protein in prion-infected cell lines and primary-cultured neurons by PrPSc-specific immunostaining.The Journal of general virology · 2016Article
- Generating Bona Fide Mammalian Prions with Internal Deletions.Journal of virology · 2016Article
- Glycoform-independent prion conversion by highly efficient, cell-based, protein misfolding cyclic amplification.Scientific reports · 2016Article
- Mutated but Not Deleted Ovine PrP(C) N-Terminal Polybasic Region Strongly Interferes with Prion Propagation in Transgenic Mice.Journal of virology · 2016Article
- Efficient inhibition of infectious prions multiplication and release by targeting the exosomal pathway.Cellular and molecular life sciences : CMLS · 2015Article
- Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie.PLoS pathogens · 2015Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The abnormally folded form of the prion protein (PrP(Sc)) accumulating in nervous and lymphoid tissues of prion-infected individuals can be naturally cleaved to generate a N-terminal-truncated fragment called C2. Information about the identity of the cellular proteases involved in this process and its possible role in prion biology has remained limited and controversial. We investigated PrP(Sc) N-terminal trimming in different cell lines and primary cultured nerve cells, and in the brain and spleen tissue from transgenic mice infected by ovine and mouse prions. We found the following: (i) the full-length to C2 ratio varies considerably depending on the infected cell or tissue. Thus, in primary neurons and brain tissue, PrP(Sc) accumulated predominantly as untrimmed species, whereas efficient trimming occurred in Rov and MovS cells, and in spleen tissue. (ii) Although C2 is generally considered to be the counterpart of the PrP(Sc) proteinase K-resistant core, the N termini of the fragments cleaved in vivo and in vitro can actually differ, as evidenced by a different reactivity toward the Pc248 anti-octarepeat antibody. (iii) In lysosome-impaired cells, the ratio of full-length versus C2 species dramatically increased, yet efficient prion propagation could occur. Moreover, cathepsin but not calpain inhibitors markedly inhibited C2 formation, and in vitro cleavage by cathepsins B and L produced PrP(Sc) fragments lacking the Pc248 epitope, strongly arguing for the primary involvement of acidic hydrolases of the endolysosomal compartment. These findings have implications on the molecular analysis of PrP(Sc) and cell pathogenesis of prion infection.
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