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. Author manuscript; available in PMC: 2016 Jun 2.
Published in final edited form as: Neuron. 2012 Dec 6;76(5):871–885. doi: 10.1016/j.neuron.2012.11.020

Figure 5. ApoE4 Displays Impaired Trafficking through the Secretory Pathway That Can Be Corrected by Blocking ApoE4 Domain Interaction.

Figure 5

Fluorescence recovery after laser photobleaching experiments were performed on EGFP-apoE3- and EGFP-apoE4-expressing Neuro-2a cells. For each section, the left and center panels show representative recovery curves for the ER and Golgi apparatus, respectively, while the right-hand panel shows quantitative histograms of apoE mobility.

(A) Recovery curves show that apoE4 trafficking is decreased compared with apoE3 in both the ER (left) and Golgi apparatus (center). Right, histogram showing that the percent of the immobile fraction was greater with apoE4 than apoE3.

(B) The impaired trafficking of apoE4 was reversed by site-directed mutagenesis of arginine-61, which blocked domain interaction (apoE4-R61T). This mutation reversed the impairment in apoE4 trafficking and mobility in both the ER and Golgi apparatus.

(C) Treatment of apoE4-expressing cells with a structure corrector (PH-002) restored the trafficking of apoE4 through the secretory pathway. The structure corrector did not affect the trafficking of apoE3 or apoE4-R61T (Brodbeck et al., 2011). Modified from Figures 3, 4, 5 originally published in Brodbeck, J., McGuire, J., Liu, Z., Meyer-Franke, A., Balestra, M.E., Jeong, D.-e., Pleiss, M., McComas, C., Hess, F., Witter, D., Peterson, S., Childers, M., Goulet, M., Liverton, N., Hargreaves, R., Freedman, S., Weisgraber, K., Mahley, R.W., Huang, Y. Structure-dependent impairment of intracellular apolipoprotein E4 trafficking and its detrimental effects are rescued by small-molecule structure correctors. J. Biol. Chem. 2011; 286:17217–17226. © the American Society for Biochemistry and Molecular Biology.