{"doi":"10.1101/2020.07.01.182360","title":"TDP-43 proteinopathy alters the ribosome association of multiple mRNAs including the glypican Dally-like protein (Dlp)/GPC6","abstract":"Abstract Amyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative disease in which 97% of patients exhibit cytoplasmic aggregates containing the RNA binding protein TDP-43. Using tagged ribosome affinity purifications in Drosophila models of TDP-43 proteinopathy, we identified TDP-43 dependent translational alterations in motor neurons impacting the spliceosome, pentose phosphate and oxidative phosphorylation pathways. A subset of the mRNAs with altered ribosome association are also enriched in TDP-43 complexes suggesting that they may be direct targets. Among these, dlp mRNA, which encodes the glypican Dally like protein (Dlp)/GPC6, a wingless (Wg/Wnt) signaling regulator is insolubilized both in flies and patient tissues with TDP-43 pathology. While Dlp/GPC6 forms puncta in the Drosophila neuropil and ALS spinal cords, it is reduced at the neuromuscular synapse in flies suggesting compartment specific effects of TDP-43 proteinopathy. These findings together with genetic interaction data show that Dlp/GPC6 is a novel, physiologically relevant target of TDP-43 proteinopathy.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":127040,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9635,"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":392263,"name":"Suvithanandhini Loganathan","orcid":"0000-0003-2608-5092","position":1,"is_corresponding":false},{"id":237810,"name":"Eric Alsop","orcid":"0000-0002-2717-7573","position":2,"is_corresponding":false},{"id":576380,"name":"Alexander D. Blythe","orcid":null,"position":3,"is_corresponding":false},{"id":576381,"name":"Tina Kovalik","orcid":null,"position":4,"is_corresponding":false},{"id":575501,"name":"Nicholas P. Mortimore","orcid":"0009-0005-5226-7094","position":5,"is_corresponding":false},{"id":576382,"name":"Dianne Barrameda","orcid":null,"position":6,"is_corresponding":false},{"id":576383,"name":"Chuol Kueth","orcid":null,"position":7,"is_corresponding":false},{"id":392264,"name":"Randall J. Eck","orcid":"0000-0003-0461-7721","position":8,"is_corresponding":false},{"id":576384,"name":"Bhavani B. Siddegowda","orcid":null,"position":9,"is_corresponding":false},{"id":576385,"name":"Archi Joardar","orcid":null,"position":10,"is_corresponding":false},{"id":575502,"name":"Hannah Ball","orcid":"0000-0003-2804-2387","position":11,"is_corresponding":false},{"id":576386,"name":"Maria E. Macias","orcid":null,"position":12,"is_corresponding":false},{"id":306876,"name":"Robert Bowser","orcid":"0000-0001-5404-7259","position":13,"is_corresponding":false},{"id":237817,"name":"Kendall Van Keuren‐Jensen","orcid":"0000-0001-8833-6323","position":14,"is_corresponding":false},{"id":392265,"name":"Daniela C. Zarnescu","orcid":"0000-0002-9607-0139","position":15,"is_corresponding":false},{"id":393886,"name":"Erik M. Lehmkuhl","orcid":null,"position":0,"is_corresponding":true}],"reference_count":123,"raw_metadata":null,"created_at":"2026-07-18T23:15:30.930746Z","pmid":null,"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":[]}