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Mercy D Pawar, Jingyu Yao, David N Zacks, Cagri G Besirli; Molecular Regulation of Fas Apoptotic Inhibitory Molecule 2 (Faim2) during photoreceptor apoptosis.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2396.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the molecular pathways regulating Fas Apoptotic Inhibitory Molecule 2 (Faim2), an intrinsic inhibitor of the Fas death receptor apoptotic pathway, during photoreceptor apoptosis.
661W cells, an in vitro cell line model of photoreceptors, were treated with Fas ligand (FasL) to activate Fas receptor signaling. Retina-retinal pigment epithelium (RPE) separation was created in wild type and Faim2 knockout mice by subretinal injection of 1% hyaluronic acid. Association of Faim2 with Fas was evaluated with immunoprecipitation. Phosphorylation of Faim2 was evaluated. Protein profiling by Mass Spectrometry was performed to identify phosphorylated sites and determine the intracellular proteins associating with Faim2 during photoreceptor stress. Long-term effect of loss of Faim2 function in photoreceptor survival was quantified in wild type and Faim2 knockout retinas isolated from 6 and 12 month old mice.
Faim2 expression was upregulated in 661W cells with Fas receptor activation in vitro and in the photoreceptors after experimental retinal detachment in vivo. Faim2 associated directly with Fas receptor complex. Photoreceptor stress led to Faim2 phosphorylation on a Serine and a Threonine residue. There was increased association of Faim2 with numerous proteins involved in apoptotic cell death after Fas receptor activation, including p53, Stat1, MAPK1, and Smn1.
Phosphorylation of Faim2 could be a key element in the down regulation of Fas-mediated apoptosis and interactions with other survival protiens.
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