{"doi":"10.1083/jcb.202102070","title":"Bro1 stimulates Vps4 to promote intralumenal vesicle formation during multivesicular body biogenesis","abstract":"Endosomal sorting complexes required for transport (ESCRT-0, -I, -II, -III) execute cargo sorting and intralumenal vesicle (ILV) formation during conversion of endosomes to multivesicular bodies (MVBs). The AAA-ATPase Vps4 regulates the ESCRT-III polymer to facilitate membrane remodeling and ILV scission during MVB biogenesis. Here, we show that the conserved V domain of ESCRT-associated protein Bro1 (the yeast homologue of mammalian proteins ALIX and HD-PTP) directly stimulates Vps4. This activity is required for MVB cargo sorting. Furthermore, the Bro1 V domain alone supports Vps4/ESCRT-driven ILV formation in vivo without efficient MVB cargo sorting. These results reveal a novel activity of the V domains of Bro1 homologues in licensing ESCRT-III-dependent ILV formation and suggest a role in coordinating cargo sorting with membrane remodeling during MVB sorting. Moreover, ubiquitin binding enhances V domain stimulation of Vps4 to promote ILV formation via the Bro1-Vps4-ESCRT-III axis, uncovering a novel role for ubiquitin during MVB biogenesis in addition to facilitating cargo recognition.","journal":"The Journal of Cell Biology","year":2021,"id":174535,"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":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":583762,"name":"Shirley Dean","orcid":null,"position":1,"is_corresponding":false},{"id":386298,"name":"Brian A. Davies","orcid":null,"position":2,"is_corresponding":false},{"id":714087,"name":"Ishara F. Azmi","orcid":"0000-0001-6280-3149","position":3,"is_corresponding":false},{"id":714088,"name":"Natalya Pashkova","orcid":"0000-0002-2191-4683","position":4,"is_corresponding":false},{"id":583765,"name":"Johanna A. Payne","orcid":null,"position":5,"is_corresponding":false},{"id":583766,"name":"Jennifer Staffenhagen","orcid":null,"position":6,"is_corresponding":false},{"id":416938,"name":"Matt West","orcid":null,"position":7,"is_corresponding":false},{"id":320789,"name":"Robert C. Piper","orcid":"0000-0001-9995-5699","position":8,"is_corresponding":false},{"id":391328,"name":"Greg Odorizzi","orcid":"0000-0002-1143-1098","position":9,"is_corresponding":false},{"id":384816,"name":"David J. Katzmann","orcid":"0000-0001-8622-343X","position":10,"is_corresponding":false},{"id":520839,"name":"Chun‐Che Tseng","orcid":"0000-0001-9637-4127","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-18T23:47:06.584146Z","pmid":"34160559","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":[]}