دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Intracellular accumulation of tau inhibits autophagosome formation by activating TIA1-amino acid-mTORC1 signaling
المؤلفون: Meng-Zhu Li, En-Jie Liu, Qiu-Zhi Zhou, Shi-Hong Li, Shi-Jie Liu, Hai-Tao Yu, Qi-Hang Pan, Fei Sun, Ting He, Wei-Jin Wang, Dan Ke, Yu-Qi Feng, Jun Li, Jian-Zhi Wang
المصدر: Military Medical Research, Vol 9, Iss 1, Pp 1-16 (2022)
بيانات النشر: BMC, 2022.
سنة النشر: 2022
المجموعة: LCC:Medicine (General)
LCC:Military Science
مصطلحات موضوعية: Tau, Autophagy, Amino acid pathway, Mammalian target of rapamycin kinase complex 1 (mTORC1), T cell intracellular antigen 1 (TIA1), Medicine (General), R5-920, Military Science
الوصف: Abstract Background Autophagy dysfunction plays a crucial role in tau accumulation and neurodegeneration in Alzheimer’s disease (AD). This study aimed to investigate whether and how the accumulating tau may in turn affect autophagy. Methods The primary hippocampal neurons, N2a and HEK293T cells with tau overexpression were respectively starved and treated with vinblastine to study the effects of tau on the initiating steps of autophagy, which was analysed by Student's two-tailed t-test. The rapamycin and concanamycin A were employed to inhibit the mammalian target of rapamycin kinase complex 1 (mTORC1) activity and the vacuolar H+-ATPase (v-ATPase) activity, respectively, which were analysed by One‐way ANOVA with post hoc tests. The Western blotting, co-immunoprecipitation and immunofluorescence staining were conducted to gain insight into the mechanisms underlying the tau effects of mTORC1 signaling alterations, as analysed by Student's two-tailed t-test or One‐way ANOVA with post hoc tests. The autophagosome formation was detected by immunofluorescence staining and transmission electron microscopy. The amino acids (AA) levels were detected by high performance liquid chromatography (HPLC). Results We observed that overexpressing human full-length wild-type tau to mimic AD-like tau accumulation induced autophagy deficits. Further studies revealed that the increased tau could bind to the prion-related domain of T cell intracellular antigen 1 (PRD-TIA1) and this association significantly increased the intercellular level of amino acids (Leucine, P = 0.0038; Glutamic acid, P = 0.0348; Alanine, P = 0.0037; Glycine, P = 0.0104), with concordant upregulation of mTORC1 activity [phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (p-4EBP1), P
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2054-9369
Relation: https://doaj.org/toc/2054-9369
DOI: 10.1186/s40779-022-00396-x
URL الوصول: https://doaj.org/article/c3d580c51c4a4c6a9ce76531a6abec8a
رقم الأكسشن: edsdoj.3d580c51c4a4c6a9ce76531a6abec8a
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20549369
DOI:10.1186/s40779-022-00396-x