Skip to main content
Fig. 6 | Military Medical Research

Fig. 6

From: Intracellular accumulation of tau inhibits autophagosome formation by activating TIA1-amino acid-mTORC1 signaling

Fig. 6

Expressing TIA1-PRD attenuates tau-induced autophagy dysfunction. a Expressing TIA1-PRD blocked tau and TIA1 binding in N2a cells detected by co-IP. b N2a cells were cotransfected with 3 × Flag-tau and GFP-PRD plasmids. Expressing TIA1-PRD attenuated tau-induced hyperphosphorylation of 4EBP1 and ULK1, which was detected by Western blotting (n = 9). c Expressing TIA1-PRD attenuated tau-induced perilysosomal aggregation of mTOR in HEK293T cells, which was imaged by immunofluorescence staining, scale bar = 20 μm. The yellow arrows point to the colocalization of LAMP1 and mTOR. d N2a cells were cotransfected with 3 × Flag-tau and GFP-PRD plasmids. Expressing TIA1-PRD recovered tau-induced dysfunction of protein synthesis, which was detected by Western blotting using anti-puromycin (n = 9). e Expressing TIA1-PRD recovered tau-induced dysfunction of autophagosome formation in HEK293T cells. The autophagosomes were imaged by immunofluorescence staining. scale bar = 5 μm. f 3 × Tg-AD mice were administered with PROTAC (C004019), and the protein level of human tau and the levels of phosphorylated p70S6K1 and ULK1 were detected by Western blotting (n = 9). 4EBP1 the eukaryotic translation initiation factor 4E-binding protein 1, BFP blue fluorescent protein, C4 C004019, GFP green fluorescent protein, IP immunoprecipitation, LAMP1 lysosome-associated membrane glycoprotein 1, LC3 microtubule-associated protein light chain 3, mTOR the mammalian target of rapamycin kinase, NC normal control, ns no significance, p70S6K1 70 kDa ribosomal protein S6 kinase 1, PRD prion-related domain, TIA1 T cell intracellular antigen 1, ULK1 unc-51-like autophagy-activating kinase 1, Vec vector, WT wild type. All data are expressed as the mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001

Back to article page