Stress Granule Assembly Can Facilitate but Is Not Required for TDP-43 Cytoplasmic Aggregation
dc.contributor.author | Fernandes, Nikita | |
dc.contributor.author | Nero, Luke | |
dc.contributor.author | Lyons, Shawn M | |
dc.contributor.author | Ivanov, Pavel | |
dc.contributor.author | Mittelmeier, Telsa M | |
dc.contributor.author | Bolger, Timothy A | |
dc.contributor.author | Buchan, J Ross | |
dc.date.accessioned | 2021-04-23T19:42:29Z | |
dc.date.available | 2021-04-23T19:42:29Z | |
dc.date.issued | 2020-09-25 | |
dc.identifier.citation | Fernandes, 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.issn | 2218-273X | |
dc.identifier.pmid | 32992901 | |
dc.identifier.doi | 10.3390/biom10101367 | |
dc.identifier.uri | http://hdl.handle.net/10150/657906 | |
dc.description.abstract | Stress 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.iso | en | en_US |
dc.publisher | MDPI | en_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.uri | https://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | TDP-43 | en_US |
dc.subject | stress granules | en_US |
dc.subject | P-bodies | en_US |
dc.title | Stress Granule Assembly Can Facilitate but Is Not Required for TDP-43 Cytoplasmic Aggregation | en_US |
dc.type | Article | en_US |
dc.identifier.eissn | 2218-273X | |
dc.contributor.department | Univ Arizona, Dept Mol & Cellular Biol | en_US |
dc.identifier.journal | BIOMOLECULES | en_US |
dc.description.note | Open access journal | en_US |
dc.description.collectioninformation | This 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.version | Final published version | en_US |
dc.source.journaltitle | Biomolecules | |
dc.source.volume | 10 | |
dc.source.issue | 10 | |
refterms.dateFOA | 2021-04-23T19:42:30Z | |
dc.source.country | United States | |
dc.source.country | United States | |
dc.source.country | United States | |
dc.source.country | United States | |
dc.source.country | United States | |
dc.source.country | Switzerland |