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Updated: May 28, 2026
High-throughput Screening for Protein-based Inheritance in S. cerevisiae
Published on: August 8, 2017
Variation in Chst8 gene expression level affects PrPC to PrPSc conversion efficiency in prion-infected Mov cells
Renaud Martin1, Sandrine Chantepie, Jérôme Chapuis
1INRA, UMR1061 Génétique Moléculaire Animale - Université de Limoges, 87060 Limoges, France.
Abstract:
The conversion of the endogenous cellular prion protein to an abnormally folded isoform is a hallmark of transmissible spongiform encephalopathies. It occurs when a misfolded prion protein contacts the cellular PrP. Among the molecular partners suggested to be involved in the misfolding process, the glycosaminoglycans seem to be good candidates. The present study was aimed to examine a possible link between PrP conversion efficiency and transcript level of Chst8 gene that encodes the carbohydrate N-acetylgalactosamine 4-O-sulfotransferase 8. Mov cells expressing ovine PrP were transfected with shRNA directed against Chst8 transcripts. Resulting clones were characterized for their Chst8 and Prnp transcript levels, and for their content in sulfated glycosaminoglycans, more particularly sulfated chondroitins. Unexpectedly, the decreased amount of Chst8 transcript induced an increase of the chondroitin sulfate percentage among total GAGs, with an increased amount of 4-O-sulfation of GalNAc residues. Upon to infection by a sheep prion, a slight amount of PrP(Sc) was observed, which rapidly disappeared upon subpassaging. Together, these findings indicate that the Chst8 transcript level affects the glycosaminoglycan environment of the cellular prion protein, and as a consequence its ability for conversion into PrP(Sc).
Insights
Altering the Chst8 gene impacts glycosaminoglycans, affecting prion protein conversion in transmissible spongiform encephalopathies. This suggests a link between Chst8 levels and prion disease susceptibility.
Area of Science:
- Neuroscience
- Biochemistry
- Molecular Biology
Background:
- Transmissible spongiform encephalopathies (TSEs) are linked to the misfolding of cellular prion protein (PrP) into abnormal isoforms.
- Glycosaminoglycans (GAGs) are implicated as potential molecular partners in the PrP misfolding process.
- The Chst8 gene encodes N-acetylgalactosamine 4-O-sulfotransferase 8, an enzyme involved in GAG synthesis.
Purpose of the Study:
- To investigate the relationship between PrP conversion efficiency and the transcript levels of the Chst8 gene.
- To understand how Chst8 influences the glycosaminoglycan environment and its role in prion protein misfolding.
Main Methods:
- Ovine PrP-expressing Mov cells were transfected with shRNA targeting Chst8 transcripts.
- Analysis of Chst8 and Prnp transcript levels in transfected cells.
- Characterization of sulfated glycosaminoglycans, specifically chondroitin sulfates, in the resulting clones.
Main Results:
- Reduced Chst8 transcript levels unexpectedly increased the proportion of chondroitin sulfate among total GAGs.
- A significant increase in 4-O-sulfation of GalNAc residues was observed in Chst8-deficient cells.
- Infection with sheep prion resulted in a transient, low level of PrP(Sc) that disappeared upon subpassaging.
Conclusions:
- Chst8 transcript levels modulate the glycosaminoglycan environment surrounding the cellular prion protein.
- This modulation, in turn, affects the prion protein's susceptibility to conversion into the pathogenic PrP(Sc) form.
- Findings suggest Chst8 plays a role in regulating prion conversion efficiency.
