{"doi":"10.1111/tra.12731","title":"<scp>ESCRT</scp> ‐dependent protein sorting is required for the viability of yeast clathrin‐mediated endocytosis mutants","abstract":"Endocytosis regulates many processes, including signaling pathways, nutrient uptake, and protein turnover. During clathrin-mediated endocytosis (CME), adaptors bind to cytoplasmic regions of transmembrane cargo proteins, and many endocytic adaptors are also directly involved in the recruitment of clathrin. This clathrin-associated sorting protein family includes the yeast epsins, Ent1/2, and AP180/PICALM homologs, Yap1801/2. Mutant strains lacking these four adaptors, but expressing an epsin N-terminal homology (ENTH) domain necessary for viability (4Δ+ENTH), exhibit endocytic defects, such as cargo accumulation at the plasma membrane (PM). This CME-deficient strain provides a sensitized background ideal for revealing cellular components that interact with clathrin adaptors. We performed a mutagenic screen to identify alleles that are lethal in 4Δ+ENTH cells using a colony-sectoring reporter assay. After isolating candidate synthetic lethal genes by complementation, we confirmed that mutations in VPS4 led to inviability of a 4Δ+ENTH strain. Vps4 mediates the final step of endosomal sorting complex required for transport (ESCRT)-dependent trafficking, and we found that multiple ESCRTs are also essential in 4Δ+ENTH cells, including Snf7, Snf8 and Vps36. Deletion of VPS4 from an end3Δ strain, another CME mutant, similarly resulted in inviability, and upregulation of a clathrin-independent endocytosis pathway rescued 4Δ+ENTH vps4Δ cells. Loss of Vps4 from an otherwise wild-type background caused multiple cargoes to accumulate at the PM because of an increase in Rcy1-dependent recycling of internalized protein to the cell surface. Additionally, vps4Δ rcy1Δ mutants exhibited deleterious growth phenotypes. Together, our findings reveal previously unappreciated effects of disrupted ESCRT-dependent trafficking on endocytic recycling and the PM.","journal":"Traffic","year":2020,"id":110981,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"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":527201,"name":"Samantha Y. Lux","orcid":"0000-0001-9749-1616","position":1,"is_corresponding":false},{"id":478238,"name":"Joanna E. Poprawski","orcid":null,"position":2,"is_corresponding":false},{"id":528117,"name":"Yorke Zhang","orcid":null,"position":3,"is_corresponding":false},{"id":268699,"name":"James L. Shepherdson","orcid":"0000-0002-3288-7000","position":4,"is_corresponding":false},{"id":528118,"name":"Pedro G. Castiñeira","orcid":null,"position":5,"is_corresponding":false},{"id":527202,"name":"Sanjana R. Pesari","orcid":"0009-0008-1743-8291","position":6,"is_corresponding":false},{"id":527203,"name":"Tony Yao","orcid":"0009-0003-6375-3712","position":7,"is_corresponding":false},{"id":527204,"name":"Derek C. Prosser","orcid":"0000-0002-6738-2758","position":8,"is_corresponding":false},{"id":528119,"name":"Carolyn Norris","orcid":null,"position":9,"is_corresponding":false},{"id":528120,"name":"Beverly Wendland","orcid":null,"position":10,"is_corresponding":false},{"id":527200,"name":"Kyle Hoban","orcid":"0000-0002-2286-6724","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-18T23:13:01.914939Z","pmid":"32255230","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":[]}