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- Ju Gao
- Department of Pharmacology and Experimental Neurosciences, University of Nebraska Medical Center, Omaha, NE 1
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- Luwen Wang
- Department of Pharmacology and Experimental Neurosciences, University of Nebraska Medical Center, Omaha, NE 1
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- Xiaojia Ren
- Department of Pharmacology and Experimental Neurosciences, University of Nebraska Medical Center, Omaha, NE 1
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- Justin R. Dunn
- Department of Pharmacology and Experimental Neurosciences, University of Nebraska Medical Center, Omaha, NE 1
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- Ariele Peters
- Department of Pharmacology and Experimental Neurosciences, University of Nebraska Medical Center, Omaha, NE 1
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- Masaru Miyagi
- Department of Pharmacology, Case Western Reserve University, Cleveland, OH 2
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- Hisashi Fujioka
- Electron Microscopy Core Facility, Case Western Reserve University, Cleveland, OH 3
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- Fangli Zhao
- Department of Neuroscience, The Ohio State University, Columbus, OH 4
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- Candice Askwith
- Department of Neuroscience, The Ohio State University, Columbus, OH 4
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- Jingjing Liang
- Department of Pathology, Case Western Reserve University, Cleveland, OH 5
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- Xinglong Wang
- Department of Pharmacology and Experimental Neurosciences, University of Nebraska Medical Center, Omaha, NE 1
抄録
<jats:p>The in vivo physiological function of liquid–liquid phase separation (LLPS) that governs non–membrane-bound structures remains elusive. Among LLPS-prone proteins, TAR DNA-binding protein of 43 kD (TDP-43) is under intense investigation because of its close association with neurological disorders. Here, we generated mice expressing endogenous LLPS-deficient murine TDP-43. LLPS-deficient TDP-43 mice demonstrate impaired neuronal function and behavioral abnormalities specifically related to brain function. Brain neurons of these mice, however, did not show TDP-43 proteinopathy or neurodegeneration. Instead, the global rate of protein synthesis was found to be greatly enhanced by TDP-43 LLPS loss. Mechanistically, TDP-43 LLPS ablation increased its association with PABPC4, RPS6, RPL7, and other translational factors. The physical interactions between TDP-43 and translational factors relies on a motif, the deletion of which abolished the impact of LLPS-deficient TDP-43 on translation. Our findings show a specific physiological role for TDP-43 LLPS in the regulation of brain function and uncover an intriguing novel molecular mechanism of translational control by LLPS.</jats:p>
収録刊行物
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- Journal of Cell Biology
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Journal of Cell Biology 220 (10), 2021-08-24
Rockefeller University Press
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キーワード
詳細情報 詳細情報について
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- CRID
- 1360861711917651968
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- ISSN
- 15408140
- 00219525
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- データソース種別
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- Crossref