{"doi":"10.3389/fnsyn.2022.1021832","title":"Protein phosphatase-1 inhibitor-2 promotes PP1γ positive regulation of synaptic transmission","abstract":"Inhibitor-2 (I-2) is a prototypic inhibitor of protein phosphatase-1 (PP1), a major serine-threonine phosphatase that regulates synaptic plasticity and learning and memory. Although I-2 is a potent inhibitor of PP1 in vitro , our previous work has elucidated that, in vivo , I-2 may act as a positive regulator of PP1. Here we show that I-2 and PP1 γ , but not PP1α, positively regulate synaptic transmission in hippocampal neurons. Moreover, we demonstrated that I-2 enhanced PP1 γ interaction with its major synaptic scaffold, neurabin, by Förster resonance energy transfer (FRET)/Fluorescence lifetime imaging microscopy (FLIM) studies, while having a limited effect on PP1 auto-inhibitory phosphorylation. Furthermore, our study indicates that the effect of I-2 on PP1 activity in vivo is dictated by I-2 threonine-72 phosphorylation. Our work thus demonstrates a molecular mechanism by which I-2 positively regulates PP1 function in synaptic transmission.","journal":"Frontiers in Synaptic Neuroscience","year":2022,"id":284095,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9537,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":961362,"name":"Haider F. Altimimi","orcid":"0000-0002-4516-141X","position":1,"is_corresponding":false},{"id":322040,"name":"Hailong Hou","orcid":null,"position":2,"is_corresponding":false},{"id":703836,"name":"Yu Zhang","orcid":"0000-0001-8938-1927","position":3,"is_corresponding":false},{"id":661109,"name":"Cody McKee","orcid":null,"position":4,"is_corresponding":false},{"id":268505,"name":"Makaía M. Papasergi-Scott","orcid":"0000-0003-3238-3213","position":5,"is_corresponding":false},{"id":647811,"name":"Hongtian Yang","orcid":"0000-0001-6754-4107","position":6,"is_corresponding":false},{"id":961848,"name":"Abigail Mayer","orcid":null,"position":7,"is_corresponding":false},{"id":961849,"name":"Nancy E. Ward","orcid":null,"position":8,"is_corresponding":false},{"id":302013,"name":"David M. MacLean","orcid":"0000-0001-8294-6075","position":9,"is_corresponding":false},{"id":21453,"name":"Angus C. Nairn","orcid":"0000-0002-7075-0195","position":10,"is_corresponding":false},{"id":961363,"name":"David Stellwagen","orcid":"0000-0003-3509-103X","position":11,"is_corresponding":false},{"id":320782,"name":"Houhui Xia","orcid":"0000-0001-6806-7736","position":12,"is_corresponding":false},{"id":660293,"name":"Karl Foley","orcid":"0000-0002-2366-0496","position":0,"is_corresponding":true}],"reference_count":29,"raw_metadata":null,"created_at":"2026-07-19T00:29:32.702533Z","pmid":"36276179","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":[]}