title: Variation in Chst8 gene expression level affects PrPC to PrPSc conversion efficiency in prion-infected Mov cells.
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).
authors: INRA, UMR1061 Génétique Moléculaire Animale - Université de Limoges, 87060 Limoges, France.
authors: Renaud
authors: R
authors: Martin
authors: Sandrine
authors: S
authors: Chantepie
authors: Jérôme
authors: J
authors: Chapuis
authors: Aurélien
authors: A
authors: Le-Duc
authors: Abderrahman
authors: A
authors: Maftah
authors: Dulcé
authors: D
authors: Papy-Garcia
authors: Hubert
authors: H
authors: Laude
authors: Jean-Michel
authors: JM
authors: Petit
authors: Paul-François
authors: PF
authors: Gallet
mesh_terms: D000818:Animals; D002460:Cell Line; D015971:Gene Expression Regulation, Enzymologic; D006025:Glycosaminoglycans / Q000378:metabolism; D051379:Mice; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism*; D012756:Sheep; D015238:Sulfotransferases / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D006025:Glycosaminoglycans; D018621:PrPC Proteins; D018620:PrPSc Proteins; C092527:N-acetylgalactosamine-4-sulfotransferase; D015238:Sulfotransferases