Tau Oligomers and Fibrils Exhibit Differential Patterns of Seeding and Association With RNA Binding Proteins
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 s...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-09-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fneur.2020.579434/full |
| _version_ | 1818341492487356416 |
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| author | Lulu Jiang Jian Zhao Ji-Xin Cheng Ji-Xin Cheng Benjamin Wolozin Benjamin Wolozin Benjamin Wolozin Benjamin Wolozin |
| author_facet | Lulu Jiang Jian Zhao Ji-Xin Cheng Ji-Xin Cheng Benjamin Wolozin Benjamin Wolozin Benjamin Wolozin Benjamin Wolozin |
| author_sort | Lulu Jiang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T15:59:39Z |
| format | Article |
| id | doaj.art-8e30992be7df4d41b2a35d9491cfd7e3 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-12-13T15:59:39Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-8e30992be7df4d41b2a35d9491cfd7e32022-12-21T23:39:13ZengFrontiers Media S.A.Frontiers in Neurology1664-22952020-09-011110.3389/fneur.2020.579434579434Tau Oligomers and Fibrils Exhibit Differential Patterns of Seeding and Association With RNA Binding ProteinsLulu Jiang0Jian Zhao1Ji-Xin Cheng2Ji-Xin Cheng3Benjamin Wolozin4Benjamin Wolozin5Benjamin Wolozin6Benjamin Wolozin7Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, United StatesBoston University Photonics Center, Boston, MA, United StatesBoston University Photonics Center, Boston, MA, United StatesCenter for Neurophotonics, Boston University School of Medicine, Boston, MA, United StatesDepartment of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, United StatesCenter for Neurophotonics, Boston University School of Medicine, Boston, MA, United StatesDepartment of Neurology, Boston University School of Medicine, Boston, MA, United StatesCenter for Systems Neuroscience, Boston University School of Medicine, Boston, MA, United StatesTau 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.https://www.frontiersin.org/article/10.3389/fneur.2020.579434/fulltau oligomerneurofibrillary tangle (NFT)image proceedingRNA translationstressstress granules |
| spellingShingle | Lulu Jiang Jian Zhao Ji-Xin Cheng Ji-Xin Cheng Benjamin Wolozin Benjamin Wolozin Benjamin Wolozin Benjamin Wolozin Tau Oligomers and Fibrils Exhibit Differential Patterns of Seeding and Association With RNA Binding Proteins Frontiers in Neurology tau oligomer neurofibrillary tangle (NFT) image proceeding RNA translation stress stress granules |
| title | Tau Oligomers and Fibrils Exhibit Differential Patterns of Seeding and Association With RNA Binding Proteins |
| title_full | Tau Oligomers and Fibrils Exhibit Differential Patterns of Seeding and Association With RNA Binding Proteins |
| title_fullStr | Tau Oligomers and Fibrils Exhibit Differential Patterns of Seeding and Association With RNA Binding Proteins |
| title_full_unstemmed | Tau Oligomers and Fibrils Exhibit Differential Patterns of Seeding and Association With RNA Binding Proteins |
| title_short | Tau Oligomers and Fibrils Exhibit Differential Patterns of Seeding and Association With RNA Binding Proteins |
| title_sort | tau oligomers and fibrils exhibit differential patterns of seeding and association with rna binding proteins |
| topic | tau oligomer neurofibrillary tangle (NFT) image proceeding RNA translation stress stress granules |
| url | https://www.frontiersin.org/article/10.3389/fneur.2020.579434/full |
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