ArticleProceedings of the National Academy of Sciences of the United States of America2017
Amyotrophic lateral sclerosis-linked mutations increase the viscosity of liquid-like TDP-43 RNP granules in neurons.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 165 papers.
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Who cites it
165 citing papers in PubMed, 265 citations in OpenAlex.
- Synaptic Proteostasis in Health and Disease.Journal of neurochemistry · 2026Review
- Nascent Extracellular Matrix Converts Biomaterial Cues into Cell Fate Decisions.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TDP-43 oxidation and PP1 crosstalk at RNA granule-mitochondria contact sites.Nature communications · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- EBF2 condensates enable adipose thermogenesis through ZFP423 sequestration and epigenetic remodeling.Nature communications · 2026Article
- Amyloid-β, Tau Protein, α-Synuclein, TDP-43, and FUS in Mixed Pathology: And Intrinsic Disorder to Rule Them All.International journal of molecular sciences · 2026Review
- The dynamic and heterogeneous composition of biomolecular condensates and its functional relevance.Nature reviews. Molecular cell biology · 2026Review
- Liquid-liquid phase separation in neural development.Cellular and molecular life sciences : CMLS · 2026Review
- TDP-43 in neurodegeneration and cancer: Decoding the mechanism of mRNA localization and translation.Biochemistry and biophysics reports · 2026Review
- Implications of virus-induced stress granules in tauopathies.Translational neurodegeneration · 2026Review
- Understanding liquid-liquid phase separation through TDP-43: fundamental principles, subcellular compartmentalisation, and role of solid inclusion formation.Genome biology · 2026Review
- From Evasion to Collapse: The Kinetic Cascade of TDP-43 and the Failure of Proteostasis.International journal of molecular sciences · 2026Review
- From TDP-43/RNA complex formation to disease-linked TDP-43 aggregation through a structural and cellular approach.Nature communications · 2026Article
- Dysregulated neuronal mRNA transport and translation in FTD/ALS.NPJ dementia · 2026Review
- Site-specific methionine oxidation alters structure and phase separation of TDP-43 C-terminal domain.bioRxiv : the preprint server for biology · 2025Article
- Muscle-derived miR-126 regulates TDP-43 axonal local synthesis and NMJ integrity in ALS models.Nature neuroscience · 2025Article
- Emergence of Compact Oligomers inside the Small-World Network of TDP-43 Condensates.The journal of physical chemistry letters · 2025Article
- RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.Molecular neurodegeneration · 2025Review
- The rheology and interfacial properties of biomolecular condensates.Biophysical reviews · 2025Review
- Molecular simulations of enzymatic phosphorylation of disordered proteins and their condensates.Nature communications · 2025Article
105 more citing papers are in PubMed but not listed here.
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4 authors at 1 institution in 1 country.
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Abstract
Ribonucleoprotein (RNP) granules are enriched in specific RNAs and RNA-binding proteins (RBPs) and mediate critical cellular processes. Purified RBPs form liquid droplets in vitro through liquid-liquid phase separation and liquid-like non-membrane-bound structures in cells. Mutations in the human RBPs TAR-DNA binding protein 43 (TDP-43) and RNA-binding protein FUS cause amyotrophic lateral sclerosis (ALS), but the biophysical properties of these proteins have not yet been studied in neurons. Here, we show that TDP-43 RNP granules in axons of rodent primary cortical neurons display liquid-like properties, including fusion with rapid relaxation to circular shape, shear stress-induced deformation, and rapid fluorescence recovery after photobleaching. RNP granules formed from wild-type TDP-43 show distinct biophysical properties depending on axonal location, suggesting maturation to a more stabilized structure is dependent on subcellular context, including local density and aging. Superresolution microscopy demonstrates that the stabilized population of TDP-43 RNP granules in the proximal axon is less circular and shows spiculated edges, whereas more distal granules are both more spherical and more dynamic. RNP granules formed by ALS-linked mutant TDP-43 are more viscous and exhibit disrupted transport dynamics. We propose these altered properties may confer toxic gain of function and reflect differential propensity for pathological transformation.
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