{"doi":"10.1016/j.celrep.2020.108538","title":"Nuclear Import Receptors Directly Bind to Arginine-Rich Dipeptide Repeat Proteins and Suppress Their Pathological Interactions","abstract":"Nuclear import receptors, also called importins, mediate nuclear import of proteins and chaperone aggregation-prone cargoes (e.g., neurodegeneration-linked RNA-binding proteins [RBPs]) in the cytoplasm. Importins were identified as modulators of cellular toxicity elicited by arginine-rich dipeptide repeat proteins (DPRs), an aberrant protein species found in C9orf72-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Mechanistically, the link between importins and arginine-rich DPRs remains unclear. Here, we show that arginine-rich DPRs (poly-GR and poly-PR) bind directly to multiple importins and, in excess, promote their insolubility and condensation. In cells, poly-GR impairs Impα/β-mediated nuclear import, including import of TDP-43, an RBP that aggregates in C9orf72-ALS/FTD patients. Arginine-rich DPRs promote phase separation and insolubility of TDP-43 in vitro and in cells, and this pathological interaction is suppressed by elevating importin concentrations. Our findings suggest that importins can decrease toxicity of arginine-rich DPRs by suppressing their pathological interactions.","journal":"Cell Reports","year":2020,"id":52879,"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":126,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.954,"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":269517,"name":"Sinem Usluer","orcid":null,"position":1,"is_corresponding":false},{"id":60678,"name":"Benjamin Bourgeois","orcid":null,"position":2,"is_corresponding":false},{"id":268282,"name":"Francesca Simonetti","orcid":"0000-0001-6437-8879","position":3,"is_corresponding":false},{"id":268283,"name":"Hana M. Odeh","orcid":"0000-0002-2164-7925","position":4,"is_corresponding":false},{"id":268284,"name":"Charlotte M. Fare","orcid":"0000-0003-0394-6435","position":5,"is_corresponding":false},{"id":269518,"name":"Mareike Czuppa","orcid":null,"position":6,"is_corresponding":false},{"id":268285,"name":"Marián Hruška-Plocháň","orcid":"0000-0002-9253-4362","position":7,"is_corresponding":false},{"id":269519,"name":"Mario Hofweber","orcid":null,"position":8,"is_corresponding":false},{"id":268286,"name":"Magdalini Polymenidou","orcid":"0000-0003-1271-9445","position":9,"is_corresponding":false},{"id":268287,"name":"James Shorter","orcid":"0000-0001-5269-8533","position":10,"is_corresponding":false},{"id":268288,"name":"Dieter Edbauer","orcid":"0000-0002-7186-4653","position":11,"is_corresponding":false},{"id":60679,"name":"Tobias Madl","orcid":"0000-0002-9725-5231","position":12,"is_corresponding":false},{"id":80179,"name":"Dorothee Dormann","orcid":"0000-0002-9260-2775","position":13,"is_corresponding":false},{"id":80164,"name":"Saskia Hutten","orcid":null,"position":0,"is_corresponding":true}],"reference_count":104,"raw_metadata":null,"created_at":"2026-07-18T20:43:25.742124Z","pmid":"33357437","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":[]}