Variation in Chst8 gene expression level affects PrPC to PrPSc conversion efficiency in prion-infected Mov cells
2011
Martin, Renaud | Chantepie, Sandrine | Chapuis, Jerome | Le Duc, Aurelien | Maftah, Abderrahman, A. | Papy-Garcia, Dulcé | Laude, Hubert | Petit, Jean-Michel | Gallet, Paul-François | Unité de Génétique Moléculaire Animale (UMR GMA) ; Université de Limoges (UNILIM)-Institut National de la Recherche Agronomique (INRA) | Croissance cellulaire, réparation et régénération tissulaires (CRRET) ; Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS) | Unité de recherche Virologie et Immunologie Moléculaires (VIM (UR 0892)) ; Institut National de la Recherche Agronomique (INRA) | This work was supported by grants from the Limoges University, the Conseil Regional of Limousin, the Institut National de la Recherche Agronomique (INRA).
Chantier qualité GA
Show more [+] Less [-]English. 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 PrPSc 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 PrPSc.
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