@article{95be9d16e25145f2ba31af71c3cc9e95,
title = "Cytoplasmic TDP-43 De-mixing Independent of Stress Granules Drives Inhibition of Nuclear Import, Loss of Nuclear TDP-43, and Cell Death",
abstract = "TDP-43 aggregation is the major hallmark of multiple neurodegenerative diseases, including ALS and FTD. Gasset-Rosa et al. demonstrate that transient stress induces long-lasting cytoplasmic TDP-43 de-mixing independent of stress granules, driving nuclear import defects, nuclear TDP-43 clearance, and cell death.",
keywords = "ALS/FTD, RNA-binding proteins, TDP-43, TDP-43 de-mixing, iPSCs, liquid-liquid phase separation, low complexity domains, motor neurons, neurodegeneration, nucleocytoplasmic transport, stress granules",
author = "Fatima Gasset-Rosa and Shan Lu and Haiyang Yu and Cong Chen and Ze'ev Melamed and Lin Guo and James Shorter and {Da Cruz}, Sandrine and Cleveland, {Don W.}",
note = "Funding Information: We would like to thank Mrs. Jennifer Santini (UCSD, Light Microscopy Core) and Mr. Timo Merlo (UCSD, Electron Microscopy Core) for resources. We thank iXCells Biotechnologies for providing human iPSC-derived motor neuron precursor cells. This work was supported by grants from the NIH (R01-NS27036 and P40-NS047101) and the Nomis Foundation. F.G.-R. is the recipient of career development awards from the Muscular Dystrophy Association and Target ALS. H.Y. is recipient of a postdoctoral fellowship from the NIH (F32-AG059358). C.C. received salary support from the ALS Association. Z.M. was recipient of a Human Frontiers Science Program (HFSP) long-term fellowship. D.W.C. and S.D.C. receive salary support from the Ludwig Institute for Cancer Research. F.G.-R. S.L. H.Y. C.C. S.D.C. and D.W.C. designed the research; F.G.-R. S.L. H.Y. C.C. S.D.C. and D.W.C. analyzed data; F.G.-R. S.L. H.Y. C.C. and Z.M. performed research; F.G.-R. conducted the experiments of fibril-induced cytoplasmic de-mixing of endogenous TDP-43. S.L. conducted the experiments of arsenite-induced TDP-43 de-mixing; F.G.-R. S.L. S.D.C. and D.W.C. wrote the text. L.G. and J.S. provided key reagents. The authors declare no competing interests. Funding Information: We would like to thank Mrs. Jennifer Santini (UCSD, Light Microscopy Core) and Mr. Timo Merlo (UCSD, Electron Microscopy Core) for resources. We thank iXCells Biotechnologies for providing human iPSC-derived motor neuron precursor cells. This work was supported by grants from the NIH ( R01-NS27036 and P40-NS047101 ) and the Nomis Foundation . F.G.-R. is the recipient of career development awards from the Muscular Dystrophy Association and Target ALS . H.Y. is recipient of a postdoctoral fellowship from the NIH ( F32-AG059358 ). C.C. received salary support from the ALS Association . Z.M. was recipient of a Human Frontiers Science Program (HFSP) long-term fellowship. D.W.C. and S.D.C. receive salary support from the Ludwig Institute for Cancer Research . Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
month = apr,
day = "17",
doi = "10.1016/j.neuron.2019.02.038",
language = "English (US)",
volume = "102",
pages = "339--357.e7",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "2",
}