{"doi":"10.1101/2022.08.19.504572","title":"Gigaxonin is required for intermediate filament transport","abstract":"Abstract Gigaxonin is an adaptor protein for E3 ubiquitin ligase substrates. It is necessary for ubiquitination and degradation of intermediate filament (IF) proteins. Giant axonal neuropathy is a pathological condition caused by mutations in the GAN gene that encodes gigaxonin. This condition is characterized by abnormal accumulation of IFs in both neuronal and non-neuronal cells; however, it is unclear what causes IF aggregation. In this work, we studied the dynamics of IFs using their subunits tagged with a photoconvertible protein mEOS 3.2. We have demonstrated that the loss of gigaxonin dramatically inhibited transport of IFs along microtubules by the microtubule motor kinesin-1. This inhibition was specific for IFs, as other kinesin-1 cargoes, with the exception of mitochondria, were transported normally. Another effect of gigaxonin loss was a more than 20-fold increase in the amount of soluble vimentin oligomers in the cytoplasm of gigaxonin knock-out cells. We speculate that these oligomers saturate a yet unidentified adapter that is required for kinesin-1 binding to IFs, which might inhibit IF transport along microtubules causing their abnormal accumulation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":310732,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":278210,"name":"James P. Zewe","orcid":"0000-0001-5086-9052","position":1,"is_corresponding":false},{"id":557814,"name":"Yuan Cheng","orcid":"0000-0003-4173-293X","position":2,"is_corresponding":false},{"id":44548,"name":"Mark Kittisopikul","orcid":"0000-0002-9558-6248","position":3,"is_corresponding":false},{"id":648699,"name":"Puneet Opal","orcid":"0000-0001-9110-2202","position":4,"is_corresponding":false},{"id":270775,"name":"Karen M. Ridge","orcid":"0000-0001-7784-0014","position":5,"is_corresponding":false},{"id":402179,"name":"Vladimir I. Gelfand","orcid":"0000-0002-6361-2798","position":6,"is_corresponding":false},{"id":1006746,"name":"Bhuvanasundar Renganathan","orcid":"0000-0003-1878-3739","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T00:33:24.451129Z","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":[]}