{"doi":"10.1242/jcs.247841","title":"TrkB deubiquitylation by USP8 regulates receptor levels and BDNF-dependent neuronal differentiation","abstract":"ABSTRACT Ubiquitylation of receptor tyrosine kinases (RTKs) regulates both the levels and functions of these receptors. The neurotrophin receptor TrkB (also known as NTRK2), a RTK, is ubiquitylated upon activation by brain-derived neurotrophic factor (BDNF) binding. Although TrkB ubiquitylation has been demonstrated, there is a lack of knowledge regarding the precise repertoire of proteins that regulates TrkB ubiquitylation. Here, we provide mechanistic evidence indicating that ubiquitin carboxyl-terminal hydrolase 8 (USP8) modulates BDNF- and TrkB-dependent neuronal differentiation. USP8 binds to the C-terminus of TrkB using its microtubule-interacting domain (MIT). Immunopurified USP8 deubiquitylates TrkB in vitro, whereas knockdown of USP8 results in enhanced ubiquitylation of TrkB upon BDNF treatment in neurons. As a consequence of USP8 depletion, TrkB levels and its activation are reduced. Moreover, USP8 protein regulates the differentiation and correct BDNF-dependent dendritic formation of hippocampal neurons in vitro and in vivo. We conclude that USP8 positively regulates the levels and activation of TrkB, modulating BDNF-dependent neuronal differentiation. This article has an associated First Person interview with the first author of the paper.","journal":"Journal of Cell Science","year":2020,"id":69491,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9467,"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":368375,"name":"Minseok Song","orcid":"0000-0001-9561-8505","position":1,"is_corresponding":false},{"id":370062,"name":"Begoña Anta","orcid":null,"position":2,"is_corresponding":false},{"id":370063,"name":"Francisco J. González-Calvo","orcid":null,"position":3,"is_corresponding":false},{"id":368376,"name":"Rubén Deogracias","orcid":"0000-0002-9279-7867","position":4,"is_corresponding":false},{"id":72604,"name":"Deqiang Jing","orcid":null,"position":5,"is_corresponding":false},{"id":72619,"name":"Francis S. Lee","orcid":"0000-0002-7108-9650","position":6,"is_corresponding":false},{"id":368377,"name":"Juan Carlos Arévalo","orcid":"0000-0003-1994-3095","position":7,"is_corresponding":false},{"id":368374,"name":"Carlos Martín‐Rodríguez","orcid":"0000-0002-9621-2133","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T21:42:48.813846Z","pmid":"33288548","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":[]}