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RNA-binding proteins (RBPs) with prion-like domains (PrLDs) phase transition to functional liquids, which can mature into aberrant hydrogels composed of pathological fibrils that underpin fatal neurodegenerative disorders. Several nuclear RBPs with PrLDs, including TDP-43, FUS, hnRNPA1, and hnRNPA2, mislocalize to cytoplasmic inclusions in neurodegenerative disorders, and mutations in their PrLDs can accelerate fibrillization and cause disease. Here, we establish that nuclear-import receptors (NIRs) specifically chaperone and potently disaggregate wild-type and disease-linked RBPs bearing a NLS. Karyopherin-β2 (also called Transportin-1) engages PY-NLSs to inhibit and reverse FUS, TAF15, EWSR1, hnRNPA1, and hnRNPA2 fibrillization, whereas Importin-α plus Karyopherin-β1 prevent and reverse TDP-43 fibrillization. Remarkably, Karyopherin-β2 dissolves phase-separated liquids and aberrant fibrillar hydrogels formed by FUS and hnRNPA1. In vivo, Karyopherin-β2 prevents RBPs with PY-NLSs accumulating in stress granules, restores nuclear RBP localization and function, and rescues degeneration caused by disease-linked FUS and hnRNPA2. Thus, NIRs therapeutically restore RBP homeostasis and mitigate neurodegeneration.
Pubmed ID: 29677512 RIS Download
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Software application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.
View all literature mentionsThis polyclonal targets ACTG1, ACTC1, ACTA1, ACTA2, ACTG2, ACTB
View all literature mentionsThis polyclonal targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal targets FUS/TLS
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis unknown targets IgG
View all literature mentionsThis monoclonal targets Transportin 1
View all literature mentionsThis polyclonal targets FUS
View all literature mentionsThis polyclonal targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis monoclonal targets hnRNP A2/B1 (EF-67)
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis unknown targets GAPDH
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal targets EIF4G1
View all literature mentionsThis monoclonal targets HA-Tag
View all literature mentionsCell line ReNcell VM is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-lacZ.B}melt[Bg4-2-4b] from BDSC.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsPublic image processing and analysis program for Macintosh.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on September 28,2023. Software application which can analyze basic Western blot data and export them for use in spreadsheet programs. Users can create standardized or custom lab reports and can share them with colleagues. Image Studio Lite has been discontinued and replaced with Empiria Studio Software.
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsThis polyclonal targets ACTG1, ACTC1, ACTA1, ACTA2, ACTG2, ACTB
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