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• W3193611512 abstract "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." @default.
• W3193611512 created "2021-08-30" @default.
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• W3193611512 date "2021-08-24" @default.
• W3193611512 modified "2023-10-15" @default.
• W3193611512 title "Translational regulation in the brain by TDP-43 phase separation" @default.
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• W3193611512 doi "https://doi.org/10.1083/jcb.202101019" @default.
• W3193611512 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8404466" @default.
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