Fig. 1
From: A novel dephosphorylation targeting chimera selectively promoting tau removal in tauopathies
DEPTAC binds to tau and simultaneously recruits PP2A-Bα. a Functional motifs and amino acid sequence of DEPTAC (DEP). b The estimated triadic interaction of DEPTAC with tau (khaki) and PP2A-Bα (cyan) based on their 3D-structures in ZDOCK Server. Key binding residues of DEPTAC were as labeled. c, d Direct interactions of FITC-conjugated DEPTAC to tau and PP2A-Bα measured by fluorescence polarization binding (c) and the competing (d) assays. e High cell penetrability of DEPTAC in cultured primary rat neurons. Scale bar, 20 μm. f No cytotoxicity of the DEPTAC (to 200 μM) detected by CCK8 assay. Data were normalized by the mean value of the 0-μM group. One-way ANOVA followed by Tukey’s multiple comparisons tests. F(4, 25) = 1.47, P = 0.24. g The triadic interaction of DEPTAC with tau and PP2A-B was confirmed by immunoprecipitation using DEPTAC antibody in primary cultured rat neurons (12 h). h Co-immunoprecipitation of DEPTAC with tau and PP2A-B can be detected 6–24 h of post-DEPTAC treatment, with a gradual decrease of total tau. i DEPTAC decreased tau phosphorylation at Ser/Thr residues with upregulated tau ubiquitination in the presence of MG132
