{"doi":"10.3390/biom10101367","title":"Stress Granule Assembly Can Facilitate but Is Not Required for TDP-43 Cytoplasmic Aggregation","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. 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.","journal":"Biomolecules","year":2020,"id":94414,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":38,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":470824,"name":"Luke Nero","orcid":null,"position":1,"is_corresponding":false},{"id":108011,"name":"Shawn M. Lyons","orcid":"0000-0002-2289-6392","position":2,"is_corresponding":false},{"id":17832,"name":"Pavel Ivanov","orcid":"0000-0002-7986-7760","position":3,"is_corresponding":false},{"id":470224,"name":"Telsa M. Mittelmeier","orcid":"0000-0003-2894-3986","position":4,"is_corresponding":false},{"id":470225,"name":"Timothy A. Bolger","orcid":"0000-0001-9526-4110","position":5,"is_corresponding":false},{"id":73366,"name":"Jillian G. Buchan","orcid":"0000-0001-9274-6173","position":6,"is_corresponding":false},{"id":470823,"name":"Nikita Fernandes","orcid":null,"position":0,"is_corresponding":true}],"reference_count":69,"raw_metadata":null,"created_at":"2026-07-18T22:32:04.778261Z","pmid":"32992901","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}