{"doi":"10.1016/j.bbamcr.2019.07.003","title":"ArhGAP12 plays dual roles in Stabilin-2 mediated efferocytosis: Regulates Rac1 basal activity and spatiotemporally turns off the Rac1 to orchestrate phagosome maturation","abstract":null,"journal":"Biochimica et Biophysica Acta (BBA) - Molecular Cell Research","year":2019,"id":658182,"datarank":0.8797895144322194,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.4304296733991207,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.4304296733991207,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":19,"citers_with_citation_signal":14,"citers_with_endowment":14,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1718136,"name":"Junyoung Seo","orcid":null,"position":1,"is_corresponding":false},{"id":1718137,"name":"Sang-Yeob Kim","orcid":null,"position":2,"is_corresponding":false},{"id":1718138,"name":"Seung-Yoon Park","orcid":null,"position":3,"is_corresponding":false},{"id":1718139,"name":"Jae Do Yoo","orcid":null,"position":4,"is_corresponding":false},{"id":1718140,"name":"Jae-Hoon Pyo","orcid":null,"position":5,"is_corresponding":false},{"id":436544,"name":"Wonhwa Cho","orcid":"0000-0003-1410-2481","position":6,"is_corresponding":false},{"id":143618,"name":"Je-Yoel Cho","orcid":null,"position":7,"is_corresponding":false},{"id":133001,"name":"Soyoun Kim","orcid":null,"position":8,"is_corresponding":false},{"id":1718142,"name":"In-San Kim","orcid":null,"position":9,"is_corresponding":false},{"id":1718135,"name":"Dong-Jun Bae","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"ArhGAP12 plays dual roles in Stabilin-2 mediated efferocytosis: Regulates Rac1 basal activity and spatiotemporally turns off the Rac1 to orchestrate phagosome maturation","abstract":"The rapid and precise clearance of apoptotic cells (efferocytosis) involves a series of phagocytic processes through which apoptotic cells are recognized, engulfed, and degraded within phagocytes. The Rho-family GTPases critically rearrange the cytoskeleton for these phagocytic processes, but we know little about the mechanisms by which regulatory proteins control the spatiotemporal activities of the Rho-family GTPases. Here, we identify ArhGAP12 as a functional GTPase-activating protein (GAP) of Rac1 during Stabilin-2 mediated efferocytosis. ArhGAP12 constitutively forms a complex with the phosphatidylserine receptor, Stabilin-2, via direct interaction with the downstream protein, GULP, but is released from the complex when Stabilin-2 interacts with apoptotic cells. When the phagocytic cup is closed and the apoptotic cell is surrounded by the phagosomal membrane, ArhGAP12 localizes to the phagocytic cup via a specific interaction with phosphatidylinositol-4,5-bisphosphate, which is transiently biosynthesized in the phagocytic cup. Down-regulation of ArhGAP12 results in sustained Rac1 activity, arrangement of F-actin, and delayed phagosome-lysosome fusion. Our results collectively suggest that ArhGAP12 carries dual roles in Stabilin-2 mediated efferocytosis: it binds to GULP/Stabilin-2 and switches off Rac1 basal activity and switches on the Rac1 by releasing itself from the complex. In addition, the spatiotemporal membrane targeting of ArhGAP12 inactivates Rac1 in a time-specific and spatially coordinated manner to orchestrate phagosome maturation. This may shed light on how other RhoGAPs spatiotemporally inactivate Rac or Cdc42 during phagocytosis by various cells, in different circumstances.","is_dataset_classified":null,"base_score":2.995732273553991,"endowment":2.995732273553991,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"31301364","pmcid":null,"openalex_id":"https://openalex.org/W2962134450","authors":[],"funders":[{"funder_name":"Ministry of Education","grant_id":"2014R1A5A2009242","title":null},{"funder_name":"Ministry of Education","grant_id":"2017R1A3B1023418","title":null},{"funder_name":"Ministry of Education","grant_id":"NRF-2018R1D1A3A03001116","title":null},{"funder_name":"Asan Institute for Life Sciences, Asan Medical Center","grant_id":"2016-585","title":null},{"funder_name":"Asan Institute for Life Sciences, Asan Medical Center","grant_id":"R35GM122530","title":null},{"funder_name":"National Research Foundation of Korea","grant_id":"","title":null},{"funder_name":"National Institutes of Health","grant_id":"","title":null}],"total_grants":7,"fwci":0.2288,"citation_percentile":0.50282208,"influential_citations":0,"citation_trend":[{"year":2020,"count":2},{"year":2022,"count":1},{"year":2023,"count":1},{"year":2024,"count":6},{"year":2025,"count":4},{"year":2026,"count":5}],"oa_status":"closed","license":"http://www.elsevier.com/open-access/userlicense/1.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0167488919301193?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0167488919301193?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.bbamcr.2019.07.003","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/31301364","host_type":"repository"}],"fields_of_study":["Phagocytosis and Immune Regulation","Erythrocyte Function and Pathophysiology","Cellular transport and secretion","Actins","Adaptor Proteins, Signal Transducing","Animals","Cell Adhesion Molecules, Neuronal","Cell Line","Down-Regulation","GTPase-Activating Proteins","Gene Knockdown Techniques","Humans","Lysosomes","Mice","Phagocytes","Phagocytosis","Phagosomes","Phosphatidylinositol 4,5-Diphosphate","rac1 GTP-Binding Protein"],"mesh_terms":["Actins","Animals","Cell Line","Humans","Lysosomes","Phagocytes","Phagocytosis","Phagosomes","Down-Regulation","Cell Adhesion Molecules, Neuronal","Phosphatidylinositol 4,5-Diphosphate","GTPase-Activating Proteins","rac1 GTP-Binding Protein","Adaptor Proteins, Signal Transducing","Mice","Gene Knockdown Techniques"],"keywords":["Efferocytosis","Phagosome","Cell biology","RAC1","Phagocytosis","Biology","GTPase","CDC42","Phosphatidylserine","Pinocytosis","Signal transduction","Cell","Macrophage","Biochemistry","Endocytosis","Membrane","Phagosome Maturation","Phosphatidylinositol-4,5-bisphosphate","Rac1 Activity","Arhgap12"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-12T03:32:01.759042Z","pmid":null,"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":[]}