The thioredoxin-like protein rod-derived cone viability factor (RdCVFL) interacts with TAU and inhibits its phosphorylation in the retina.
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.
Fridlich
Ram
R
double daggerInstitut de la Vision, INSERM UMR592, 17 rue Moreau, 75012 Paris, France.
Delalande
Francois
F
Jaillard
Céline
C
Lu
Jun
J
Poidevin
Laetitia
L
Cronin
Thérèse
T
Perrocheau
Ludivine
L
Millet-Puel
Géraldine
G
Niepon
Marie-Laure
ML
Poch
Olivier
O
Holmgren
Arne
A
Van Dorsselaer
Alain
A
Sahel
Jose-Alain
JA
Léveillard
Thierry
T
D000818:Animals; D002460:Cell Line; D002853:Chromatography, Liquid; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018384:Oxidative Stress; D010766:Phosphorylation; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D012160:Retina / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
D005136:Eye Proteins; D020033:Protein Isoforms; C525119:RdCVF protein, mouse; D016875:tau Proteins; D013879:Thioredoxins