Tau Oligomers and Fibrils Exhibit Differential Patterns of Seeding and Association With RNA Binding Proteins.
Tau Oligomers and Fibrils Exhibit Differential Patterns of Seeding and Association With RNA Binding Proteins.
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DOI：
10.3389/fneur.2020.579434
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发表时间：
2020
影响因子：
3.4
通讯作者：
Wolozin B
中科院分区：
文献类型：
--
作者：
Jiang L;Zhao J;Cheng JX;Wolozin B
Tau蛋白聚集体是多效性的，在构象、结构和大小上表现出差异。这些聚集体是内源性的，但在疾病中也在神经元中繁殖。我们在表达人类4R0N tau的原代神经元培养物中使用播种试验，探索了两种不同类型的tau聚集体，tau寡聚物（oTau）和tau原纤维（fTau）的作用。我们发现oTau和fTau在神经元中引发不同的tau包涵体模式和不同的分子相互作用。外源性的oTau和fTau都能迅速从神经元中清除，但它们也会在细胞内播下由内源性tau组成的包涵体。这两种类型的种子在种子摄取和产生的细胞内包涵体数量方面产生不同的剂量-反应关系。免疫细胞化学研究表明，由oTau组成的种子与胁迫颗粒相关的RNA结合蛋白的共定位要比由fTau组成的种子大得多。相反，fTau与p62/SQSTM1和硫黄氨酸S的共定位要比oTau大得多。这些结果表明，oTau种子内含物可以调节翻译应激反应，具有生理活性，而fTau种子内含物是纤维状的，并被分流到自溶酶体级联。
Tau aggregates are pleiotropic and exhibit differences in conformation, structure, and size. These aggregates develop endogenously but are also propagated among neurons in disease. We explored the actions of two distinct types of tau aggregates, tau oligomers (oTau) and tau fibrils (fTau), using a seeding assay in primary neuron cultures expressing human 4R0N tau. We find that oTau and fTau elicit distinct patterns of tau inclusions in the neurons and distinct molecular interactions. The exogenously applied oTau and fTau both clear rapidly from the neurons, but both also seed intracellular inclusions composed of endogenously produced tau. The two types of seeds elicit differential dose–response relationships for seed uptake and the number of resulting intracellular inclusions. Immunocytochemical studies show that co-localization with RNA binding proteins associated with stress granules is much greater for seeds composed of oTau than fTau. Conversely, co-localization with p62/SQSTM1 and thioflavine S is much greater for fTau than oTau. These results suggest that oTau seeds inclusions that modulate the translational stress response and are physiologically active, whereas fTau seeds inclusions that are fibrillar and shunted to the autolysosomal cascade.
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影响因子：
4.3
作者：
Fischer, Nicholas W.;Prodeus, Aaron;Gariepy, Jean
通讯作者：
Gariepy, Jean
RNA结合蛋白与小tau蛋白质的含量共定位。
影响因子：
7.1
作者：
Maziuk BF;Apicco DJ;Cruz AL;Jiang L;Ash PEA;da Rocha EL;Zhang C;Yu WH;Leszyk J;Abisambra JF;Li H;Wolozin B
通讯作者：
Wolozin B
影响因子：
5.3
作者：
Rocher, A. B.;Crimins, J. L.;Amatrudo, J. M.;Kinson, M. S.;Todd-Brown, M. A.;Lewis, J.;Luebke, J. I.
通讯作者：
Luebke, J. I.
影响因子：
12.7
作者：
Jiang, Lulu;Ash, Peter E. A.;Wolozin, Benjamin
通讯作者：
Wolozin, Benjamin
影响因子：
56.9
作者：
SantaCruz, K;Lewis, J;Ashe, KH
通讯作者：
Ashe, KH