Fiche publication
Date publication
juin 2009
Auteurs
Membres identifiés du Cancéropôle Est :
Dr POCH Olivier
,
Dr VAN DORSSELAER Alain
Tous les auteurs :
Fridlich R, Delalande F, Jaillard C, Lu J, Poidevin L, Cronin T, Perrocheau L, Millet-Puel G, Niepon ML, Poch O, Holmgren A, Van Dorsselaer A, Sahel JA, Leveillard T
Lien Pubmed
Résumé
Rod-derived cone viability factor (RdCVF) is produced by the Nxnl1 gene that codes for a second polypeptide, RdCVFL, by alternative splicing. Although the role of RdCVF in promoting cone survival has been described, the implication of RdCVFL, a putative thioredoxin enzyme, in the protection of photoreceptors is presently unknown. Using a proteomics approach we identified 90 proteins interacting with RdCVFL including the microtubule-binding protein TAU. We demonstrate that the level of phosphorylation of TAU is increased in the retina of the Nxnl1(-/-) mice as it is hyperphosphorylated in the brain of patients suffering from Alzheimer disease, presumably in some cases through oxidative stress. Using a cell-based assay, we show that RdCVFL inhibits TAU phosphorylation. In vitro, RdCVFL protects TAU from oxidative damage. Photooxidative stress is implicated in retinal degeneration, particularly in retinitis pigmentosa, where it is considered to be a contributor to secondary cone death. The functional interaction between RdCVFL and TAU described here is the first characterization of the RdCVFL signaling pathway involved in neuronal cell death mediated by oxidative stress.
Référence
Mol Cell Proteomics. 2009 Jun;8(6):1206-18
