{"doi":"10.1101/2020.08.12.248401","title":"Shared and divergent phase separation and aggregation properties of brain-expressed ubiquilins","abstract":"Abstract The brain-expressed ubiquilins, UBQLNs 1, 2 and 4, are highly homologous proteins that participate in multiple aspects of protein homeostasis and are implicated in neurodegenerative diseases. Studies have established that UBQLN2 forms liquid-like condensates and accumulates in pathogenic aggregates, much like other proteins linked to neurodegenerative diseases. However, the relative condensate and aggregate formation of the three brain-expressed ubiquilins is unknown. We report that the three ubiquilins differ in aggregation propensity, revealed by in-vitro experiments, cellular models, and analysis of human brain tissue. UBQLN4 displays heightened aggregation propensity over the other ubiquilins and, like amyloids, UBQLN4 forms ThioflavinT-positive fibrils in vitro . Measuring fluorescence recovery after photobleaching (FRAP) of puncta in cells, we report that all three ubiquilins undergo liquid-liquid phase transition. UBQLN2 and 4 exhibit slower recovery than UBQLN1, suggesting the condensates formed by the brain-expressed ubiquilins have different compositions and undergo distinct internal rearrangements. We conclude that while all brain-expressed ubiquilins exhibit self-association behavior manifesting as condensates, they follow distinct courses of phase-separation and levels of aggregation. This variability among ubiquilins along the continuum from liquid-like to solid likely informs both the normal ubiquitin-linked functions of ubiquilins and their accumulation and potential contribution to toxicity in various neurodegenerative diseases.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":130678,"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":0.9491,"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":575138,"name":"Hunter Linton","orcid":null,"position":1,"is_corresponding":false},{"id":583437,"name":"Jiazheng Xing","orcid":"0000-0001-7280-249X","position":2,"is_corresponding":false},{"id":583438,"name":"Alexandra Sutter","orcid":"0000-0003-1410-8605","position":3,"is_corresponding":false},{"id":583926,"name":"Fayth S. Kakos","orcid":null,"position":4,"is_corresponding":false},{"id":583927,"name":"Jaimie H. Ryou","orcid":null,"position":5,"is_corresponding":false},{"id":583928,"name":"Nyjerus Liggans","orcid":null,"position":6,"is_corresponding":false},{"id":398350,"name":"Lisa M. Sharkey","orcid":"0000-0002-6518-3392","position":7,"is_corresponding":false},{"id":398347,"name":"Nathaniel Safren","orcid":"0000-0003-4866-4837","position":8,"is_corresponding":false},{"id":331940,"name":"Henry L. Paulson","orcid":"0000-0002-0382-7535","position":9,"is_corresponding":false},{"id":256238,"name":"Magdalena I. Ivanova","orcid":"0000-0002-7290-3327","position":10,"is_corresponding":false},{"id":398346,"name":"Julia E. Gerson","orcid":"0000-0001-5972-6138","position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T23:15:56.698770Z","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":[]}