ArticlePLoS pathogens2019
GPI-anchor signal sequence influences PrPC sorting, shedding and signalling, and impacts on different pathomechanistic aspects of prion disease in mice.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Convergent Synthesis of a Bifunctional GPI as a Universal Platform to Access Diverse GPI and GPI-Anchored Protein Probes.Organic letters · 2026Article
- Are Signal Peptides Hidden Regulators of Neurodegenerative Disease?Biomedicines · 2026Review
- Cellular prion protein and its derived peptides: multifaceted roles in neurodegenerative diseases and potential as biomarkers.Cell & bioscience · 2026Review
- Investigation of Intercellular Trafficking of Global Glycosylphosphatidylinositol-Anchored Proteins Using Cell Metabolic Engineering and Transwell Coculture.Angewandte Chemie (International ed. in English) · 2026Article
- Molecular Mechanisms and Therapeutic Potential of Degron-Mediated Proteostasis Regulation in Neurodegenerative Diseases.Cellular and molecular neurobiology · 2026Review
- Role of cellular prion protein in mouse granulosa cells and its effects on ovarian function in knockout mice.Molecular medicine reports · 2025Article
- Partial Deletion of the Carboxyl-Terminal Signal Sequence of the Cellular Prion Protein Alters Protein Expression via Endoplasmic Reticulum-Associated Degradation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Therapeutic Trajectories in Human Prion Diseases.Sub-cellular biochemistry · 2025Review
- Sorting of GPI-anchored proteins at the trypanosome surface is independent of GPI insertion signals.Cell surface (Amsterdam, Netherlands) · 2024Article
- Perspectives on CRISPR Genome Editing to Prevent Prion Diseases in High-Risk Individuals.Biomedicines · 2024Article
- A Biotinylated Glycosylphosphatidylinositol (GPI) as the Universal Platform To Access GPI-Anchored Protein Analogues.The Journal of organic chemistry · 2024Article
- Article
- Inducing prion protein shedding as a neuroprotective and regenerative approach in pathological conditions of the brain: from theory to facts.Neural regeneration research · 2023Review
- (Patho)Physiology of Glycosylphosphatidylinositol-Anchored Proteins I: Localization at Plasma Membranes and Extracellular Compartments.Biomolecules · 2023Review
- A point mutation in GPI-attachment signal peptide accelerates the development of prion disease.Acta neuropathologica · 2023Article
- Cell biology of prion strains in vivo and in vitro.Cell and tissue research · 2023Review
- Anchorless risk or released benefit? An updated view on the ADAM10-mediated shedding of the prion protein.Cell and tissue research · 2023Review
- Major Surface Antigens in ZoonoticPathogens (Basel, Switzerland) · 2022Review
- What is the role of lipids in prion conversion and disease?Frontiers in molecular neuroscience · 2022Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cellular prion protein (PrPC) is a cell surface glycoprotein attached to the membrane by a glycosylphosphatidylinositol (GPI)-anchor and plays a critical role in transmissible, neurodegenerative and fatal prion diseases. Alterations in membrane attachment influence PrPC-associated signaling, and the development of prion disease, yet our knowledge of the role of the GPI-anchor in localization, processing, and function of PrPC in vivo is limited We exchanged the PrPC GPI-anchor signal sequence of for that of Thy-1 (PrPCGPIThy-1) in cells and mice. We show that this modifies the GPI-anchor composition, which then lacks sialic acid, and that PrPCGPIThy-1 is preferentially localized in axons and is less prone to proteolytic shedding when compared to PrPC. Interestingly, after prion infection, mice expressing PrPCGPIThy-1 show a significant delay to terminal disease, a decrease of microglia/astrocyte activation, and altered MAPK signaling when compared to wild-type mice. Our results are the first to demonstrate in vivo, that the GPI-anchor signal sequence plays a fundamental role in the GPI-anchor composition, dictating the subcellular localization of a given protein and, in the case of PrPC, influencing the development of prion disease.
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