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R. Fridlich, L. Perrocheau, F. Delalande, W. Raffelsberger, O. Poch, A. Van Dorsselaer, J.-A. Sahel, T. Léveillard; The Interaction Between RdCVF and Tau Defines a Novel Signalisation Pathway in Photoreceptor Degeneration and Survival. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2993. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
RdCVF is a thioredoxin-like protein, derived from rods, that has the potential to rescue cone cells. The RdCVF long form (RdCVFL) has a putative thiol-oxidoreductase activity whereas the short one (RdCVF) is shown to act directly on cone photoreceptor survival. Identification of RdCVFL protein partners will enable us to understand the functional role of RdCVFL and its relation to cone rescue
We have used a proteomic approach in order to identify RdCVFL protein partner candidates. Soluble protein lysate from chicken retina was loaded on GST-RdCVFL and GST columns. The eluted proteins were identified by MS/MS spectrometry. The interaction was validated by Cos-1 transfection followed by Co-immunoprecipitations
We identified 79 proteins that bind specifically to GST-RdCVFL. Among them, we focused on the protein Tau, because of its involvement in neurodegeneration diseases including Alzheimer. The interaction between RdCVFL and HA-tagged chicken Tau has been validated by Co-immuprecipitation. Microtubule associated protein (MAP) Tau is abnormally hyperphosphorylated in Alzheimer's disease (AD) and related tauopathies. This modified form of Tau is the major protein of paired helical filaments (PHFs)/neurofibrillary tangles (NFTs) which lead to aggregations and neuronal cell death. The interaction between Tau and RdCVFL may relate the observation that oxidative stress induces Tau hyperphosphorylation with the potential thiol-oxidoreductase activity of RdCVFL. Furthermore, this interaction may be fundamental to the process of cone degeneration in RP and allied retinal degenerations. We have analyzed the level of hyperphosphorylated Tau in RdCVF KO mice retina by western blotting. We found that Tau hyperphosphorylation is increased in RdCVF KO mice as compared with wild-type controls
The interaction between RdCVFL, a thioredoxin-like protein and Tau is suggested to be intimately linked to the regulation of the redox status and hyperphosphorylation of Tau, the aggregation of paired helical filaments and as a result to photoreceptors survival
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