{"doi":"10.1016/j.celrep.2025.116472","title":"Poly-ubiquitylated transmembrane proteins outcompete other cargo for limited space inside clathrin-coated vesicles","abstract":"Endocytic recycling of transmembrane proteins is essential to cellular function. The intracellular domains of transmembrane proteins are frequently ubiquitylated, a modification that is recognized by adaptor proteins during clathrin-mediated endocytosis. Recent work suggests that transmembrane proteins compete for space within highly crowded endocytic structures, suggesting that enhanced internalization of one group of transmembrane proteins may come at the expense of others. Here, we show that preferential internalization of poly-ubiquitylated transmembrane proteins can result in reduced endocytosis of mono-ubiquitylated and non-ubiquitylated proteins. Further, poly-ubiquitylated receptors significantly outcompeted their less ubiquitylated counterparts for uptake of extracellular ligands. These findings suggest that clathrin-coated vesicles may act as selective filters, prioritizing highly ubiquitylated transmembrane proteins for uptake while leaving others behind. Given that poly-ubiquitylation is thought to signal protein aging and damage, these findings suggest a mechanism for selective internalization of high priority cargo, with simultaneously exclusion and protection of functional proteins lacking poly-ubiquitylation.","journal":"Cell Reports","year":2025,"id":579099,"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":0.9413,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1359132,"name":"Susovan Sarkar","orcid":"0000-0001-9083-6407","position":1,"is_corresponding":false},{"id":1359131,"name":"Yuan Feng","orcid":"0000-0002-2067-5916","position":2,"is_corresponding":false},{"id":1053463,"name":"Grant Ashby","orcid":null,"position":3,"is_corresponding":false},{"id":568014,"name":"Carl C. Hayden","orcid":null,"position":4,"is_corresponding":false},{"id":274235,"name":"Jon M. Huibregtse","orcid":"0000-0002-9210-3343","position":5,"is_corresponding":false},{"id":402451,"name":"Jeanne C. Stachowiak","orcid":"0000-0003-2501-142X","position":6,"is_corresponding":false},{"id":1359130,"name":"Haoyang Liu","orcid":"0000-0003-3891-9066","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T02:58:30.282164Z","pmid":"41201087","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":[]}