{"doi":"10.1016/j.celrep.2024.114841","title":"WWC2 modulates GABAA-receptor-mediated synaptic transmission, revealing class-specific mechanisms of synapse regulation by WWC family proteins","abstract":"The WW and C2 domain-containing protein (WWC2) is implicated in several neurological disorders. Here, we demonstrate that WWC2 interacts with inhibitory, but not excitatory, postsynaptic scaffolds, consistent with prior proteomic identification of WWC2 as a putative component of the inhibitory postsynaptic density. Using mice lacking WWC2 expression in excitatory forebrain neurons, we show that WWC2 suppresses γ-aminobutyric acid type-A receptor (GABA A R) incorporation into the plasma membrane and regulates HAP1 and GRIP1, which form a complex promoting GABA A R recycling to the membrane. Inhibitory synaptic transmission is increased in CA1 pyramidal cells lacking WWC2. Furthermore, unlike the WWC2 homolog KIBRA (kidney/brain protein; WWC1), a key regulator of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking at excitatory synapses, the deletion of WWC2 does not affect synaptic AMPAR expression. In contrast, loss of KIBRA does not affect GABA A R membrane expression. These data reveal synapse class-selective functions for WWC proteins as regulators of ionotropic neurotransmitter receptors and provide insight into mechanisms regulating GABA A R membrane expression.","journal":"Cell Reports","year":2024,"id":450763,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9645,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1118283,"name":"Julia R. Wilkerson","orcid":"0000-0002-7497-2270","position":1,"is_corresponding":false},{"id":561996,"name":"Richard C. Johnson","orcid":"0000-0003-1476-467X","position":2,"is_corresponding":false},{"id":275418,"name":"Richard L. Huganir","orcid":"0000-0001-9783-5183","position":3,"is_corresponding":false},{"id":569153,"name":"Lenora J. Volk","orcid":"0000-0002-9074-4091","position":4,"is_corresponding":false},{"id":904710,"name":"Thomas Dunham","orcid":null,"position":0,"is_corresponding":true}],"reference_count":92,"raw_metadata":null,"created_at":"2026-07-19T02:02:28.969209Z","pmid":"39388350","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":[]}