Journal: Neuron
Article Title: Apolipoprotein E4 impairs neuronal insulin signaling by trapping insulin receptor in the endosomes
doi: 10.1016/j.neuron.2017.09.003
Figure Lengend Snippet: (A and B) The interaction between IR and recombinant apoE (A) or astrocyte-secreted lipidated apoE particles (B) were evaluated by solid-phase binding assay (three independent experiments). The Kd values of the binding curves were calculated using the one-site specific binding equation. (C) The interaction between IR and recombinant apoE was evaluated by solution binding assay, followed by immunoprecipitation (IP) of apoE and immunoblotting (IB) of IR. The ratio of IR to apoE was calculated. The values were normalized to apoE3 for comparison. (D–E) The domain interaction between apoE and IR was determined by solid-phase binding assay (three independent experiments) using C-terminal truncated apoE3 or apoE4 containing the aminol acid (aa) 1-186 compared with the full-length (FL) of apoE. The values were normalized to the binding of apoE FL for comparison. (F) A competitive inhibition assay of insulin (8 nM), IR (80 nM) and apoE (4, 8, or 16 μg/ml) was analyzed using solid-phase binding assay (three independent experiments). Results were normalized to the maximal binding of insulin and IR in the absence of apoE. (G–K) Primary Apoe−/− neurons were treated overnight with recombinant apoE3 or apoE4 (100 nM) in the presence or absence of insulin (100 nM) stimulation for 30 minutes, followed by cell surface biotinylation assay and Western blot analysis (three independent experiments). The cell surface IR and total IR were shown and the ratio of cell surface IR/total IR was calculated (G, H). The values were normalized to the vehicle-treated group (V) for comparison. The change in cell surface IR/total IR after insulin treatment was evaluated (I). The amount of p-Akt (Ser473), total Akt and β-actin was detected by Western blotting (G, J, K). Ratio of p-Akt to total Akt (J) and insulin-induced p-Akt/Akt change (K) were calculated. The values were normalized to vehicle without insulin treatment group for comparison. All data represent mean ± SEM. Two-tailed student’s t test (A–C, F, I, K) and one-way ANOVA with Tukey’s multiple comparisons test (D, E, H, J) were used in for statistical analysis. *p < 0.05; **p < 0.01; N.S., not significant. Molecular mass markers in kilodaltons are shown.
Article Snippet: For apoE ELISA, WUE4 capture antibody (Novus) and biotin-conjugated mouse monoclonal K74180B detector antibody (Meridian Life Science) were used as described ( Fu et al., 2016 ).
Techniques: Recombinant, Binding Assay, Solution Binding Assay, Immunoprecipitation, Western Blot, Comparison, Inhibition, Cell Surface Biotinylation Assay, Two Tailed Test