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dc.contributor.authorFernandes, Nikita
dc.contributor.authorNero, Luke
dc.contributor.authorLyons, Shawn M
dc.contributor.authorIvanov, Pavel
dc.contributor.authorMittelmeier, Telsa M
dc.contributor.authorBolger, Timothy A
dc.contributor.authorBuchan, J Ross
dc.date.accessioned2021-04-23T19:42:29Z
dc.date.available2021-04-23T19:42:29Z
dc.date.issued2020-09-25
dc.identifier.citationFernandes, N., Nero, L., Lyons, S. M., Ivanov, P., Mittelmeier, T. M., Bolger, T. A., & Buchan, J. R. (2020). Stress Granule Assembly Can Facilitate but Is Not Required for TDP-43 Cytoplasmic Aggregation. Biomolecules, 10(10), 1367.en_US
dc.identifier.issn2218-273X
dc.identifier.pmid32992901
dc.identifier.doi10.3390/biom10101367
dc.identifier.urihttp://hdl.handle.net/10150/657906
dc.description.abstractStress granules (SGs) are hypothesized to facilitate TAR DNA-binding protein 43 (TDP-43) cytoplasmic mislocalization and aggregation, which may underly amyotrophic lateral sclerosis pathology. However, much data for this hypothesis is indirect. Additionally, whether P-bodies (PBs; related mRNA-protein granules) affect TDP-43 phenotypes is unclear. Here, we determine that induction of TDP-43 expression in yeast results in the accumulation of SG-like foci that in >90% of cases become the sites where TDP-43 cytoplasmic foci first appear. Later, TDP-43 foci associate less with SGs and more with PBs, though independent TDP-43 foci also accumulate. However, depleting or over-expressing yeast SG and PB proteins reveals no consistent trend between SG or PB assembly and TDP-43 foci formation, toxicity or protein abundance. In human cells, immunostaining endogenous TDP-43 with different TDP-43 antibodies reveals distinct localization and aggregation behaviors. Following acute arsenite stress, all phospho-TDP-43 foci colocalize with SGs. Interestingly, in SG assembly mutant cells (G3BP1/2ΔΔ), TDP-43 is enriched in nucleoli. Finally, formation of TDP-43 cytoplasmic foci following low-dose chronic arsenite stress is impaired, but not completely blocked, in G3BP1/2ΔΔ cells. Collectively, our data suggest that SG and PB assembly may facilitate TDP-43 cytoplasmic localization and aggregation but are likely not essential for these events.en_US
dc.language.isoenen_US
dc.publisherMDPIen_US
dc.rights© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.subjectTDP-43en_US
dc.subjectstress granulesen_US
dc.subjectP-bodiesen_US
dc.titleStress Granule Assembly Can Facilitate but Is Not Required for TDP-43 Cytoplasmic Aggregationen_US
dc.typeArticleen_US
dc.identifier.eissn2218-273X
dc.contributor.departmentUniv Arizona, Dept Mol & Cellular Biolen_US
dc.identifier.journalBIOMOLECULESen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.journaltitleBiomolecules
dc.source.volume10
dc.source.issue10
refterms.dateFOA2021-04-23T19:42:30Z
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countrySwitzerland


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© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Except where otherwise noted, this item's license is described as © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).