{"doi":"10.1093/genetics/iyac102","title":"The <i>Caenorhabditis elegans</i> ASPP homolog APE-1 is a junctional protein phosphatase 1 modulator","abstract":"How serine/threonine phosphatases are spatially and temporally tuned by regulatory subunits is a fundamental question in cell biology. Ankyrin repeat, SH3 domain, proline-rich-region-containing proteins are protein phosphatase 1 catalytic subunit binding partners associated with cardiocutaneous diseases. Ankyrin repeat, SH3 domain, proline-rich-region-containing proteins localize protein phosphatase 1 catalytic subunit to cell-cell junctions, but how ankyrin repeat, SH3 domain, proline-rich-region-containing proteins localize and whether they regulate protein phosphatase 1 catalytic subunit activity in vivo is unclear. Through a Caenorhabditis elegans genetic screen, we find that loss of the ankyrin repeat, SH3 domain, proline-rich-region-containing protein homolog, APE-1, suppresses a pathology called \"jowls,\" providing us with an in vivo assay for APE-1 activity. Using immunoprecipitations and mass spectrometry, we find that APE-1 binds the protein phosphatase 1 catalytic subunit called GSP-2. Through structure-function analysis, we discover that APE-1's N-terminal half directs the APE-1-GSP-2 complex to intercellular junctions. Additionally, we isolated mutations in highly conserved residues of APE-1's ankyrin repeats that suppress jowls yet do not preclude GSP-2 binding, implying APE-1 does more than simply localize GSP-2. Indeed, in vivo reconstitution of APE-1 suggests the ankyrin repeats modulate phosphatase output, a function we find to be conserved among vertebrate homologs.","journal":"Genetics","year":2022,"id":263283,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"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":919777,"name":"Derek T Wei","orcid":"0000-0001-6510-4458","position":1,"is_corresponding":false},{"id":919778,"name":"Erika Beyrent","orcid":"0000-0003-2949-1547","position":2,"is_corresponding":false},{"id":919779,"name":"Ying Zhang","orcid":"0000-0001-5519-6854","position":3,"is_corresponding":false},{"id":919780,"name":"Jian Zheng","orcid":"0000-0001-6128-026X","position":4,"is_corresponding":false},{"id":920249,"name":"Mari M. K. Camacho","orcid":null,"position":5,"is_corresponding":false},{"id":232489,"name":"Laurence Florens","orcid":"0000-0002-9310-6650","position":6,"is_corresponding":false},{"id":869860,"name":"Gunther Hollopeter","orcid":"0000-0002-6409-0530","position":7,"is_corresponding":false},{"id":919776,"name":"Gwendolyn M. Beacham","orcid":"0000-0001-7158-6887","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T00:26:29.321923Z","pmid":"35792852","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":[]}