The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Cytoplasmic TDP-43 De-mixing Independent of Stress Granules Drives Inhibition of Nuclear Import, Loss of Nuclear TDP-43, and Cell Death
Open accessAbstract
While cytoplasmic aggregation of TDP-43 is a pathological hallmark of amyotrophic lateral sclerosis and frontotemporal dementia, how aggregates form and what drives its nuclear clearance have not been determined. Here we show that TDP-43 at its endogenous level undergoes liquid-liquid phase separation (LLPS) within nuclei in multiple cell types. Increased concentration of TDP-43 in the cytoplasm or transient exposure to sonicated amyloid-containing fibrils is shown to provoke long-lived liquid droplets of cytosolic TDP-43 whose assembly and maintenance are independent of conventional stress granules. Cytosolic liquid droplets of TDP-43 accumulate phosphorylated TDP-43 and rapidly convert into gels/solids in response to transient, arsenite-mediated stress. Cytoplasmic TDP-43 droplets slowly recruit importin-α and Nup62 and induce mislocalization of RanGap1, Ran, and Nup107, thereby provoking inhibition of nucleocytoplasmic transport, clearance of nuclear TDP-43, and cell death. These findings identify a neuronal cell death mechanism that can be initiated by transient-stress induced cytosolic de-mixing of TDP-43.
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Cites
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong, L., Ran, F. A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P. D., Wu, X., Jiang, W., Marraffini, L. A., et al. (2013) · Science · doi:10.1126/science.1231143 · Cited by 15,339
Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., et al. (2006) · Science · doi:10.1126/science.1134108 · Cited by 6,576
TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis
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Converging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis
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“These two progressive neurodegenerative diseases, which share genetic and pathological features (Ling et al., 2013), are without effective treatments to slow fatal disease progression (Taylor et al.”
Self-citationLong pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43
Polymenidou, M., Lagier-Tourenne, C., Hutt, K. R., Huelga, S. C., Moran, J., Liang, T. Y., Ling, S.-C., Sun, E., Wancewicz, E., Mazur, C., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2779 · Cited by 1,335
Self-citationThe C9orf72 repeat expansion disrupts nucleocytoplasmic transport.
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GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport
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Melamed, Z., López-Erauskin, J., Baughn, M. W., Zhang, O., Drenner, K., Sun, Y., Freyermuth, F., McMahon, M. A., Beccari, M. S., Artates, J. W., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0293-z · Cited by 635
Self-citation
Cited by
Biomolecular condensates at the nexus of cellular stress, protein aggregation disease and ageing
Alberti, S., & Hyman, A. A. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-00326-6 · Cited by 1,160
Stress granules and neurodegeneration
Wolozin, B., & Ivanov, P. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0222-5 · Cited by 810
Phase separation and neurodegenerative diseases: a disturbance in the force
Zbinden, A., Pérez-Berlanga, M., De Rossi, P., & Polymenidou, M. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.09.014 · Cited by 500
Lu, S., Ye, Q., Singh, D., Cao, Y., Diedrich, J. K., Yates, J. R., Villa, E., Cleveland, D. W., & Corbett, K. D. (2021) · Nature Communications · doi:10.1038/s41467-020-20768-y · Cited by 462
Self-citationThe role of TDP-43 mislocalization in amyotrophic lateral sclerosis
Suk, T. R., & Rousseaux, M. W. C. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00397-1 · Cited by 450
Metadata
- Authors
- Gasset-Rosa, F., Lu, S., Yu, H., Chen, C., Melamed, Z., Guo, L., Shorter, J., Da Cruz, S., & Cleveland, D. W.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 102
- Issue
- 2
- Pages
- 339-357.e7
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2921912860
- Cited by
- 509
- References
- 14
- FWCI
- 33.71
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Cytoplasmic TDP-43 De-mixing Independent of Stress Granules Drives Inhibition of Nuclear Import, Loss of Nuclear TDP-43, and Cell Death. https://app.cochat.ai/papers/10.1016/j.neuron.2019.02.038
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- Gasset-Rosa, F., Lu, S., Yu, H., Chen, C., Melamed, Z., Guo, L., Shorter, J., Da Cruz, S., & Cleveland, D. W. (2019). Cytoplasmic TDP-43 De-mixing Independent of Stress Granules Drives Inhibition of Nuclear Import, Loss of Nuclear TDP-43, and Cell Death. Neuron. https://doi.org/10.1016/j.neuron.2019.02.038
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
