ArticleMolecular and cellular neurosciences2008
Pathogenic mutations in the glycosylphosphatidylinositol signal peptide of PrP modulate its topology in neuroblastoma cells.
Article in Molecular and cellular neurosciences, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Are Signal Peptides Hidden Regulators of Neurodegenerative Disease?Biomedicines · 2026Review
- M232R Familial Creutzfeldt-Jacob Disease Challenging to Diagnose Due to the Absence of Characteristic Laboratory Findings.Internal medicine (Tokyo, Japan) · 2026Article
- Lycopene: A Potent Antioxidant with Multiple Health Benefits.Journal of nutrition and metabolism · 2024Review
- Characterization of mutations inNeuropsychiatric disease and treatment · 2018Review
- Detection of misfolded protein aggregates from a clinical perspective.Journal of clinical and translational research · 2016Review
- Iron in neurodegenerative disorders of protein misfolding: a case of prion disorders and Parkinson's disease.Antioxidants & redox signaling · 2014Review
- Structural features within the nascent chain regulate alternative targeting of secretory proteins to mitochondria.The EMBO journal · 2013Article
- Residues surrounding the glycosylphosphatidylinositol anchor attachment site of PrP modulate prion infection: insight from the resistance of rabbits to prion disease.Journal of virology · 2010Article
- Redox control of prion and disease pathogenesis.Antioxidants & redox signaling · 2010Review
- Ovine reference materials and assays for prion genetic testing.BMC veterinary research · 2010Article
- The consequences of pathogenic mutations to the human prion protein.Protein engineering, design & selection : PEDS · 2009Review
- Cytosolic prion protein is the predominant anti-Bax prion protein form: exclusion of transmembrane and secreted prion protein forms in the anti-Bax function.Biochimica et biophysica acta · 2008Article
- Article
- Cytosolically expressed PrP GPI-signal peptide interacts with mitochondria.Communicative & integrative biologyArticle
- Article
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Authors and funding
4 authors.
Funding
Abstract
Point mutations M232R (PrP(232R)), M232T (PrP(232T)), and P238S (PrP(238S)) in the glycosylphosphatidylinositol signal peptide (GPI-SP) of the prion protein (PrP(C)) segregate with familial Creutzfeldt-Jakob disease (CJD). However, the mechanism by which these mutations induce cytotoxicity is unclear since the GPI-SP is replaced by a GPI anchor within 5 min of PrP synthesis and translocation into the endoplasmic reticulum (ER). To examine if mutations in this region interfere with translocation of nascent PrP into the ER or anchor addition, the metabolism of PrP(232R) and PrP(232T) was investigated in transfected human neuroblastoma cells. In this report, we demonstrate that PrP mutations M232R and M232T do not interfere with GPI anchor addition. Instead, these mutations increase the stability and transport of GPI-SP mediated post-translationally translocated PrP to the plasma membrane, where it is linked to the lipid bilayer in a potentially neurotoxic C-transmembrane ((Ctm)PrP) orientation. Furthermore, we demonstrate that the GPI-SP of PrP functions as an efficient co-translational and inefficient post-translational ER translocation signal when tagged to an unrelated protein, underscoring the functional versatility of this peptide. These data uncover an alternate pathway of ER translocation for nascent PrP, and provide information on the possible mechanism(s) of neurotoxicity by mutations in the GPI-SP.
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