{"gene":"CORO1B","run_date":"2026-06-09T22:57:19","timeline":{"discoveries":[{"year":1998,"finding":"CORO1B (coronin-2) was identified as a member of a conserved family of actin-binding proteins containing five WD repeat domains; it is ubiquitously expressed in mice and humans, consistent with a broad role in actin-dependent cellular processes.","method":"cDNA cloning, sequence analysis, expression profiling across tissues","journal":"DNA and cell biology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — structural domain identification replicated across mouse and human ESTs, single lab, sequence-based method","pmids":["9778037"],"is_preprint":false},{"year":1999,"finding":"CORO1B (coronin-2) was identified as an actin-binding protein associated with macrophage phagosomes, localizing to phagosomes in LPS-primed murine peritoneal macrophages.","method":"Monoclonal antibody screen against purified Fc receptor-mediated phagosomes; immunofluorescence and antigen identification","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single lab, antibody-based localization to phagosomes with antigen identification, no functional rescue","pmids":["10574718"],"is_preprint":false},{"year":2011,"finding":"Coro1b loss augments FcεRI-mediated mast cell degranulation: Coro1a−/− mast cells show hyperdegranulation that is further increased by additional loss of Coro1b, establishing that Coro1b contributes to an inhibitory constraint on secretory lysosome exocytosis. In vivo, Coro1a/Coro1b double-knockout mice displayed enhanced passive cutaneous anaphylaxis.","method":"Genetic knockout (single and double Coro1a/Coro1b KO mice); bone marrow-derived mast cell degranulation assays; in vivo passive cutaneous anaphylaxis; functional reconstitution assays linking cortical localization and F-actin binding to inhibitory function","journal":"The Journal of experimental medicine","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic double-KO with in vitro and in vivo phenotypic readouts, functional reconstitution linking localization and actin-binding to activity, replicated across multiple assays","pmids":["21844203"],"is_preprint":false},{"year":2012,"finding":"PDGF induces phosphorylation of Coro1B on serine-2 via PKCε in vascular smooth muscle cells (VSMCs), which reduces Coro1B interaction with the ARP2/3 complex and promotes lamellipodial protrusion and cell migration. A phosphodeficient S2A mutant of Coro1B reduces PDGF-induced migration. Coro1B phosphorylation is increased after vessel injury in vivo.","method":"siRNA knockdown; kymograph analysis of lamellipodia dynamics; co-immunoprecipitation of Coro1B with ARP2/3; phosphorylation mutant transfection (S2A); PKCε inhibition; in vivo rat/mouse vascular injury model","journal":"Circulation research","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, phosphodeficient mutant rescue, in vivo validation, multiple orthogonal methods in single lab","pmids":["22619279"],"is_preprint":false},{"year":2013,"finding":"The Wilms' tumor suppressor WT1 directly binds GC-rich sequences within the Coro1b promoter and transcriptionally regulates Coro1b expression in the epicardium. Loss of Wt1 in mouse embryos reduces Coronin 1B expression in the remaining epicardium.","method":"Promoter deletion analysis; chromatin immunoprecipitation / direct binding assays; Wt1 knockout mouse embryos; immunofluorescence localization","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct promoter binding demonstrated, validated in Wt1 KO embryos, single lab","pmids":["23562652"],"is_preprint":false},{"year":2020,"finding":"Coro1B localizes to VE-cadherin-based cell-cell junctions in endothelial cells and is recruited to actin-driven membrane protrusions at these junctions via a mechanism requiring relaxation of the actomyosin cytoskeleton. Depletion of Coro1B disrupts actin cytoskeleton and cell-cell junction organization and reduces endothelial network complexity, tube number, and tube length. Coro1B interactome analysis identified integrin-linked kinase (ILK) as a new Coro1B-associated protein, and Coro1B co-localizes with α-parvin at lamellipodia leading edges.","method":"Immunofluorescence; live-cell imaging; siRNA knockdown; co-immunoprecipitation / interactome analysis; matrigel tube formation assay","journal":"Frontiers in cell and developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — live imaging, Co-IP interactome, KD phenotype with functional readout, single lab, multiple orthogonal methods","pmids":["32850828"],"is_preprint":false},{"year":2022,"finding":"Coro1B and Coro1C co-localize with Arp2/3-branched actin and require Arp2/3 activity for proper subcellular localization. Loss of both coronins increases branched actin density and reduces actin turnover within lamellipodia, causing defective haptotaxis. Unexpectedly, coronin null cells accumulate excessive cofilin in lamellipodia alongside elevated F-actin levels, inconsistent with prior models of coronin-cofilin interaction. Loss of coronins also increases cellular contractility.","method":"Conditional double-knockout cell line (Coro1B/Coro1C); live-cell fluorescence imaging; Arp2/3 inhibition; F-actin quantification; haptotaxis assays; cofilin localization analysis","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — conditional double-KO with multiple orthogonal assays (imaging, F-actin quantification, haptotaxis, contractility), mechanistic pathway placement via Arp2/3 dependency","pmids":["35657370"],"is_preprint":false},{"year":2025,"finding":"Coro1B is a substrate of the deubiquitinase USP45: USP45 physically interacts with Coro1B, deubiquitinates it, and stabilizes its protein levels. Ablation of USP45 or Coro1B promotes F-actin patch formation and translocation of V-ATPase to lysosomes in an N-WASP-dependent manner, activating autophagy and enhancing lysosomal acidification.","method":"Co-immunoprecipitation; deubiquitination assay; siRNA/genetic knockout of USP45 and Coro1B in Drosophila and mammalian cells; F-actin imaging; lysosomal V-ATPase localization assay; N-WASP dependency epistasis","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — biochemical deubiquitination assay, Co-IP, epistasis with N-WASP, validated in two organisms (Drosophila and mammalian cells), multiple orthogonal methods","pmids":["40067150"],"is_preprint":false}],"current_model":"CORO1B is a WD-repeat actin-binding protein that localizes to Arp2/3-branched actin networks at lamellipodia and cell-cell junctions, where it promotes branched actin turnover by working in concert with cofilin; it inhibits ARP2/3 complex activity (an interaction disrupted by PKCε-mediated phosphorylation of Ser-2, which is required for PDGF-induced cell migration), restrains mast cell degranulation via cortical F-actin organization, controls endothelial junction remodeling and network assembly (partly through an ILK interaction), and is stabilized post-translationally by the deubiquitinase USP45, which suppresses autophagy by preventing F-actin patch-driven V-ATPase translocation to lysosomes."},"narrative":{"mechanistic_narrative":"CORO1B is a ubiquitously expressed WD-repeat actin-binding protein that regulates the turnover and architecture of Arp2/3-branched actin networks at the leading edge and at cell-cell junctions [PMID:9778037, PMID:35657370]. It localizes to Arp2/3-dependent branched actin in lamellipodia, and loss of CORO1B (together with CORO1C) increases branched-actin density, reduces actin turnover, impairs haptotaxis, and raises cellular contractility [PMID:35657370]. CORO1B restrains migration in part by binding and inhibiting the ARP2/3 complex; PKCε-mediated phosphorylation of Ser-2 downstream of PDGF weakens the CORO1B–ARP2/3 interaction to license lamellipodial protrusion and cell migration in vascular smooth muscle, an event also detected after vessel injury in vivo [PMID:22619279]. Through its control of cortical F-actin organization, CORO1B contributes to an inhibitory constraint on FcεRI-driven mast cell degranulation and anaphylaxis [PMID:21844203], and it organizes actin and VE-cadherin-based endothelial junctions and network assembly, where its interactome includes integrin-linked kinase (ILK) [PMID:32850828]. CORO1B protein stability is set post-translationally by the deubiquitinase USP45, which binds and deubiquitinates CORO1B; loss of either factor drives N-WASP-dependent F-actin patch formation and V-ATPase translocation to lysosomes, activating autophagy [PMID:40067150]. Its expression is transcriptionally controlled by WT1, which binds the Coro1b promoter in the epicardium [PMID:23562652].","teleology":[{"year":1998,"claim":"Established CORO1B as a member of a conserved WD-repeat actin-binding protein family, framing it as a candidate regulator of actin-dependent processes.","evidence":"cDNA cloning, sequence analysis, and expression profiling across mouse and human tissues","pmids":["9778037"],"confidence":"Medium","gaps":["No functional assay tying the domains to a specific actin activity","Ubiquitous expression does not localize function to any pathway"]},{"year":1999,"claim":"Linked CORO1B to a specific actin-dependent structure by showing it associates with macrophage phagosomes, the first subcellular localization clue.","evidence":"Monoclonal antibody screen against purified Fc receptor phagosomes with immunofluorescence in murine macrophages","pmids":["10574718"],"confidence":"Medium","gaps":["Localization only, no loss-of-function phenotype","Mechanism of phagosomal recruitment unknown"]},{"year":2011,"claim":"Showed CORO1B serves an inhibitory function in secretory exocytosis, defining a physiological role in immune cell biology.","evidence":"Single and double Coro1a/Coro1b knockout mice with mast cell degranulation assays, in vivo passive cutaneous anaphylaxis, and reconstitution linking cortical localization and actin binding to activity","pmids":["21844203"],"confidence":"High","gaps":["Degree of functional overlap versus distinct roles of Coro1a and Coro1b not fully separated","Molecular link between cortical F-actin organization and granule exocytosis not detailed"]},{"year":2012,"claim":"Identified the regulatory switch controlling CORO1B inhibition of ARP2/3, connecting a growth-factor kinase cascade to migration.","evidence":"siRNA knockdown, kymography, reciprocal Co-IP of Coro1B with ARP2/3, S2A phosphodeficient mutant rescue, PKCε inhibition, and an in vivo vascular injury model","pmids":["22619279"],"confidence":"High","gaps":["Structural basis of the CORO1B–ARP2/3 interaction not resolved","Whether Ser-2 phosphorylation governs CORO1B function outside VSMCs unknown"]},{"year":2013,"claim":"Placed CORO1B expression under direct transcriptional control of WT1, embedding it in an epicardial developmental program.","evidence":"Promoter deletion analysis, direct binding/ChIP assays, and Wt1 knockout mouse embryos with immunofluorescence","pmids":["23562652"],"confidence":"Medium","gaps":["Functional consequence of WT1-driven Coro1b expression for epicardial biology not tested","Other transcriptional inputs not assessed"]},{"year":2020,"claim":"Extended CORO1B function to endothelial junction remodeling and network assembly and named ILK as a new associated protein.","evidence":"Immunofluorescence, live imaging, siRNA knockdown, Co-IP interactome, and matrigel tube formation assays in endothelial cells","pmids":["32850828"],"confidence":"Medium","gaps":["Whether the ILK interaction is direct and functionally required not established","Recruitment mechanism via actomyosin relaxation not mechanistically dissected"]},{"year":2022,"claim":"Defined CORO1B's core mechanism as promoting branched-actin turnover and revealed an unexpected disconnect from the canonical coronin-cofilin model.","evidence":"Conditional Coro1B/Coro1C double-knockout cells with live imaging, Arp2/3 inhibition, F-actin quantification, haptotaxis, and cofilin localization analysis","pmids":["35657370"],"confidence":"High","gaps":["Mechanism reconciling cofilin accumulation with reduced turnover unresolved","Relative contributions of CORO1B versus CORO1C not separated"]},{"year":2025,"claim":"Revealed post-translational stabilization of CORO1B by USP45 and its role in suppressing autophagy via control of F-actin patch and V-ATPase dynamics.","evidence":"Co-IP, deubiquitination assay, USP45/Coro1B knockout in Drosophila and mammalian cells, F-actin imaging, lysosomal V-ATPase localization, and N-WASP epistasis","pmids":["40067150"],"confidence":"High","gaps":["Ubiquitin ligase that opposes USP45 on CORO1B not identified","Direct molecular link between CORO1B and F-actin patch suppression not fully defined"]},{"year":null,"claim":"How CORO1B simultaneously inhibits ARP2/3 yet promotes branched-actin turnover, and how its distinct roles across migration, junctions, secretion, and autophagy are coordinated, remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No structural model of CORO1B bound to ARP2/3 or F-actin","Unifying biochemical mechanism reconciling inhibition versus turnover-promotion absent","Tissue-specific functional partitioning between coronin paralogs unclear"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,1,2,6]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[3,6]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[3,5,6]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[2,5]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[1]}],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[7]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[2]}],"complexes":[],"partners":["ARPC (ARP2/3 COMPLEX)","ILK","USP45","PRKCE","PARVA","WASL"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9BR76","full_name":"Coronin-1B","aliases":["Coronin-2"],"length_aa":489,"mass_kda":54.2,"function":"Regulates leading edge dynamics and cell motility in fibroblasts. May be involved in cytokinesis and signal transduction (By similarity)","subcellular_location":"Cytoplasm, cytoskeleton; Cytoplasm, cytoskeleton, stress fiber","url":"https://www.uniprot.org/uniprotkb/Q9BR76/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CORO1B","classification":"Not Classified","n_dependent_lines":3,"n_total_lines":1208,"dependency_fraction":0.0024834437086092716},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000172725","cell_line_id":"CID000519","localizations":[{"compartment":"membrane","grade":3},{"compartment":"vesicles","grade":2}],"interactors":[{"gene":"HIST2H2AA3;HIST2H2AC","stoichiometry":0.2},{"gene":"HIST1H2BN;HIST1H2BM;HIST1H2BH;HIST2H2BF;HIST1H2BC;HIST1H2BD;HIST1H2BK;H2BFS","stoichiometry":0.2},{"gene":"CORO1C","stoichiometry":0.2},{"gene":"PARP1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000519","total_profiled":1310},"omim":[{"mim_id":"612119","title":"TREHALASE DEFICIENCY","url":"https://www.omim.org/entry/612119"},{"mim_id":"609849","title":"CORONIN 1B; CORO1B","url":"https://www.omim.org/entry/609849"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Plasma membrane","reliability":"Supported"},{"location":"Cytosol","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CORO1B"},"hgnc":{"alias_symbol":["coronin-2"],"prev_symbol":[]},"alphafold":{"accession":"Q9BR76","domains":[{"cath_id":"2.130.10.10","chopping":"15-380","consensus_level":"medium","plddt":96.9334,"start":15,"end":380}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BR76","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BR76-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9BR76-F1-predicted_aligned_error_v6.png","plddt_mean":89.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CORO1B","jax_strain_url":"https://www.jax.org/strain/search?query=CORO1B"},"sequence":{"accession":"Q9BR76","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9BR76.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9BR76/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9BR76"}},"corpus_meta":[{"pmid":"26330360","id":"PMC_26330360","title":"Whole genome and transcriptome sequencing of matched primary and peritoneal metastatic gastric carcinoma.","date":"2015","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/26330360","citation_count":81,"is_preprint":false},{"pmid":"19389958","id":"PMC_19389958","title":"Identification of internal control genes for quantitative polymerase chain reaction in mammary tissue of lactating cows receiving lipid supplements.","date":"2009","source":"Journal of dairy science","url":"https://pubmed.ncbi.nlm.nih.gov/19389958","citation_count":74,"is_preprint":false},{"pmid":"9778037","id":"PMC_9778037","title":"Definition of family of coronin-related proteins conserved between humans and mice: close genetic linkage between coronin-2 and CD45-associated protein.","date":"1998","source":"DNA and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/9778037","citation_count":55,"is_preprint":false},{"pmid":"21844203","id":"PMC_21844203","title":"Differential regulation of mast cell degranulation versus cytokine secretion by the actin regulatory proteins Coronin1a and Coronin1b.","date":"2011","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/21844203","citation_count":54,"is_preprint":false},{"pmid":"30867049","id":"PMC_30867049","title":"Impact of chemotherapy for breast cancer on leukocyte DNA methylation landscape and cognitive function: a prospective study.","date":"2019","source":"Clinical epigenetics","url":"https://pubmed.ncbi.nlm.nih.gov/30867049","citation_count":37,"is_preprint":false},{"pmid":"10574718","id":"PMC_10574718","title":"Isolation and characterization of monoclonal antibodies directed against novel components of macrophage phagosomes.","date":"1999","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/10574718","citation_count":37,"is_preprint":false},{"pmid":"25454514","id":"PMC_25454514","title":"Profilin-1 overexpression in MDA-MB-231 breast cancer cells is associated with alterations in proteomics biomarkers of cell proliferation, survival, and motility as revealed by global proteomics analyses.","date":"2014","source":"Omics : a journal of integrative biology","url":"https://pubmed.ncbi.nlm.nih.gov/25454514","citation_count":30,"is_preprint":false},{"pmid":"22619279","id":"PMC_22619279","title":"Role of coronin 1B in PDGF-induced migration of vascular smooth muscle cells.","date":"2012","source":"Circulation research","url":"https://pubmed.ncbi.nlm.nih.gov/22619279","citation_count":25,"is_preprint":false},{"pmid":"33991177","id":"PMC_33991177","title":"Cancer stem cell marker DCLK1 reprograms small extracellular vesicles toward migratory phenotype in gastric cancer cells.","date":"2021","source":"Proteomics","url":"https://pubmed.ncbi.nlm.nih.gov/33991177","citation_count":25,"is_preprint":false},{"pmid":"35657370","id":"PMC_35657370","title":"Coro1B and Coro1C regulate lamellipodia dynamics and cell motility by tuning branched actin turnover.","date":"2022","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/35657370","citation_count":21,"is_preprint":false},{"pmid":"23562652","id":"PMC_23562652","title":"The Wilms' tumor suppressor Wt1 regulates Coronin 1B expression in the epicardium.","date":"2013","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/23562652","citation_count":10,"is_preprint":false},{"pmid":"27858746","id":"PMC_27858746","title":"MicroRNA and mRNA Expression Changes in Steroid Naïve and Steroid Treated DMD Patients.","date":"2015","source":"Journal of neuromuscular diseases","url":"https://pubmed.ncbi.nlm.nih.gov/27858746","citation_count":10,"is_preprint":false},{"pmid":"32850828","id":"PMC_32850828","title":"Coronin 1B Controls Endothelial Actin Dynamics at Cell-Cell Junctions and Is Required for Endothelial Network Assembly.","date":"2020","source":"Frontiers in cell and developmental 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identified as a member of a conserved family of actin-binding proteins containing five WD repeat domains; it is ubiquitously expressed in mice and humans, consistent with a broad role in actin-dependent cellular processes.\",\n      \"method\": \"cDNA cloning, sequence analysis, expression profiling across tissues\",\n      \"journal\": \"DNA and cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — structural domain identification replicated across mouse and human ESTs, single lab, sequence-based method\",\n      \"pmids\": [\"9778037\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"CORO1B (coronin-2) was identified as an actin-binding protein associated with macrophage phagosomes, localizing to phagosomes in LPS-primed murine peritoneal macrophages.\",\n      \"method\": \"Monoclonal antibody screen against purified Fc receptor-mediated phagosomes; immunofluorescence and antigen identification\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, antibody-based localization to phagosomes with antigen identification, no functional rescue\",\n      \"pmids\": [\"10574718\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Coro1b loss augments FcεRI-mediated mast cell degranulation: Coro1a−/− mast cells show hyperdegranulation that is further increased by additional loss of Coro1b, establishing that Coro1b contributes to an inhibitory constraint on secretory lysosome exocytosis. In vivo, Coro1a/Coro1b double-knockout mice displayed enhanced passive cutaneous anaphylaxis.\",\n      \"method\": \"Genetic knockout (single and double Coro1a/Coro1b KO mice); bone marrow-derived mast cell degranulation assays; in vivo passive cutaneous anaphylaxis; functional reconstitution assays linking cortical localization and F-actin binding to inhibitory function\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic double-KO with in vitro and in vivo phenotypic readouts, functional reconstitution linking localization and actin-binding to activity, replicated across multiple assays\",\n      \"pmids\": [\"21844203\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"PDGF induces phosphorylation of Coro1B on serine-2 via PKCε in vascular smooth muscle cells (VSMCs), which reduces Coro1B interaction with the ARP2/3 complex and promotes lamellipodial protrusion and cell migration. A phosphodeficient S2A mutant of Coro1B reduces PDGF-induced migration. Coro1B phosphorylation is increased after vessel injury in vivo.\",\n      \"method\": \"siRNA knockdown; kymograph analysis of lamellipodia dynamics; co-immunoprecipitation of Coro1B with ARP2/3; phosphorylation mutant transfection (S2A); PKCε inhibition; in vivo rat/mouse vascular injury model\",\n      \"journal\": \"Circulation research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, phosphodeficient mutant rescue, in vivo validation, multiple orthogonal methods in single lab\",\n      \"pmids\": [\"22619279\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"The Wilms' tumor suppressor WT1 directly binds GC-rich sequences within the Coro1b promoter and transcriptionally regulates Coro1b expression in the epicardium. Loss of Wt1 in mouse embryos reduces Coronin 1B expression in the remaining epicardium.\",\n      \"method\": \"Promoter deletion analysis; chromatin immunoprecipitation / direct binding assays; Wt1 knockout mouse embryos; immunofluorescence localization\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct promoter binding demonstrated, validated in Wt1 KO embryos, single lab\",\n      \"pmids\": [\"23562652\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Coro1B localizes to VE-cadherin-based cell-cell junctions in endothelial cells and is recruited to actin-driven membrane protrusions at these junctions via a mechanism requiring relaxation of the actomyosin cytoskeleton. Depletion of Coro1B disrupts actin cytoskeleton and cell-cell junction organization and reduces endothelial network complexity, tube number, and tube length. Coro1B interactome analysis identified integrin-linked kinase (ILK) as a new Coro1B-associated protein, and Coro1B co-localizes with α-parvin at lamellipodia leading edges.\",\n      \"method\": \"Immunofluorescence; live-cell imaging; siRNA knockdown; co-immunoprecipitation / interactome analysis; matrigel tube formation assay\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — live imaging, Co-IP interactome, KD phenotype with functional readout, single lab, multiple orthogonal methods\",\n      \"pmids\": [\"32850828\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Coro1B and Coro1C co-localize with Arp2/3-branched actin and require Arp2/3 activity for proper subcellular localization. Loss of both coronins increases branched actin density and reduces actin turnover within lamellipodia, causing defective haptotaxis. Unexpectedly, coronin null cells accumulate excessive cofilin in lamellipodia alongside elevated F-actin levels, inconsistent with prior models of coronin-cofilin interaction. Loss of coronins also increases cellular contractility.\",\n      \"method\": \"Conditional double-knockout cell line (Coro1B/Coro1C); live-cell fluorescence imaging; Arp2/3 inhibition; F-actin quantification; haptotaxis assays; cofilin localization analysis\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — conditional double-KO with multiple orthogonal assays (imaging, F-actin quantification, haptotaxis, contractility), mechanistic pathway placement via Arp2/3 dependency\",\n      \"pmids\": [\"35657370\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Coro1B is a substrate of the deubiquitinase USP45: USP45 physically interacts with Coro1B, deubiquitinates it, and stabilizes its protein levels. Ablation of USP45 or Coro1B promotes F-actin patch formation and translocation of V-ATPase to lysosomes in an N-WASP-dependent manner, activating autophagy and enhancing lysosomal acidification.\",\n      \"method\": \"Co-immunoprecipitation; deubiquitination assay; siRNA/genetic knockout of USP45 and Coro1B in Drosophila and mammalian cells; F-actin imaging; lysosomal V-ATPase localization assay; N-WASP dependency epistasis\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — biochemical deubiquitination assay, Co-IP, epistasis with N-WASP, validated in two organisms (Drosophila and mammalian cells), multiple orthogonal methods\",\n      \"pmids\": [\"40067150\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CORO1B is a WD-repeat actin-binding protein that localizes to Arp2/3-branched actin networks at lamellipodia and cell-cell junctions, where it promotes branched actin turnover by working in concert with cofilin; it inhibits ARP2/3 complex activity (an interaction disrupted by PKCε-mediated phosphorylation of Ser-2, which is required for PDGF-induced cell migration), restrains mast cell degranulation via cortical F-actin organization, controls endothelial junction remodeling and network assembly (partly through an ILK interaction), and is stabilized post-translationally by the deubiquitinase USP45, which suppresses autophagy by preventing F-actin patch-driven V-ATPase translocation to lysosomes.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CORO1B is a ubiquitously expressed WD-repeat actin-binding protein that regulates the turnover and architecture of Arp2/3-branched actin networks at the leading edge and at cell-cell junctions [#0, #6]. It localizes to Arp2/3-dependent branched actin in lamellipodia, and loss of CORO1B (together with CORO1C) increases branched-actin density, reduces actin turnover, impairs haptotaxis, and raises cellular contractility [#6]. CORO1B restrains migration in part by binding and inhibiting the ARP2/3 complex; PKCε-mediated phosphorylation of Ser-2 downstream of PDGF weakens the CORO1B–ARP2/3 interaction to license lamellipodial protrusion and cell migration in vascular smooth muscle, an event also detected after vessel injury in vivo [#3]. Through its control of cortical F-actin organization, CORO1B contributes to an inhibitory constraint on FcεRI-driven mast cell degranulation and anaphylaxis [#2], and it organizes actin and VE-cadherin-based endothelial junctions and network assembly, where its interactome includes integrin-linked kinase (ILK) [#5]. CORO1B protein stability is set post-translationally by the deubiquitinase USP45, which binds and deubiquitinates CORO1B; loss of either factor drives N-WASP-dependent F-actin patch formation and V-ATPase translocation to lysosomes, activating autophagy [#7]. Its expression is transcriptionally controlled by WT1, which binds the Coro1b promoter in the epicardium [#4].\"\n,\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Established CORO1B as a member of a conserved WD-repeat actin-binding protein family, framing it as a candidate regulator of actin-dependent processes.\",\n      \"evidence\": \"cDNA cloning, sequence analysis, and expression profiling across mouse and human tissues\",\n      \"pmids\": [\"9778037\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional assay tying the domains to a specific actin activity\", \"Ubiquitous expression does not localize function to any pathway\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Linked CORO1B to a specific actin-dependent structure by showing it associates with macrophage phagosomes, the first subcellular localization clue.\",\n      \"evidence\": \"Monoclonal antibody screen against purified Fc receptor phagosomes with immunofluorescence in murine macrophages\",\n      \"pmids\": [\"10574718\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Localization only, no loss-of-function phenotype\", \"Mechanism of phagosomal recruitment unknown\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Showed CORO1B serves an inhibitory function in secretory exocytosis, defining a physiological role in immune cell biology.\",\n      \"evidence\": \"Single and double Coro1a/Coro1b knockout mice with mast cell degranulation assays, in vivo passive cutaneous anaphylaxis, and reconstitution linking cortical localization and actin binding to activity\",\n      \"pmids\": [\"21844203\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Degree of functional overlap versus distinct roles of Coro1a and Coro1b not fully separated\", \"Molecular link between cortical F-actin organization and granule exocytosis not detailed\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Identified the regulatory switch controlling CORO1B inhibition of ARP2/3, connecting a growth-factor kinase cascade to migration.\",\n      \"evidence\": \"siRNA knockdown, kymography, reciprocal Co-IP of Coro1B with ARP2/3, S2A phosphodeficient mutant rescue, PKCε inhibition, and an in vivo vascular injury model\",\n      \"pmids\": [\"22619279\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of the CORO1B–ARP2/3 interaction not resolved\", \"Whether Ser-2 phosphorylation governs CORO1B function outside VSMCs unknown\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Placed CORO1B expression under direct transcriptional control of WT1, embedding it in an epicardial developmental program.\",\n      \"evidence\": \"Promoter deletion analysis, direct binding/ChIP assays, and Wt1 knockout mouse embryos with immunofluorescence\",\n      \"pmids\": [\"23562652\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of WT1-driven Coro1b expression for epicardial biology not tested\", \"Other transcriptional inputs not assessed\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Extended CORO1B function to endothelial junction remodeling and network assembly and named ILK as a new associated protein.\",\n      \"evidence\": \"Immunofluorescence, live imaging, siRNA knockdown, Co-IP interactome, and matrigel tube formation assays in endothelial cells\",\n      \"pmids\": [\"32850828\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether the ILK interaction is direct and functionally required not established\", \"Recruitment mechanism via actomyosin relaxation not mechanistically dissected\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Defined CORO1B's core mechanism as promoting branched-actin turnover and revealed an unexpected disconnect from the canonical coronin-cofilin model.\",\n      \"evidence\": \"Conditional Coro1B/Coro1C double-knockout cells with live imaging, Arp2/3 inhibition, F-actin quantification, haptotaxis, and cofilin localization analysis\",\n      \"pmids\": [\"35657370\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism reconciling cofilin accumulation with reduced turnover unresolved\", \"Relative contributions of CORO1B versus CORO1C not separated\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Revealed post-translational stabilization of CORO1B by USP45 and its role in suppressing autophagy via control of F-actin patch and V-ATPase dynamics.\",\n      \"evidence\": \"Co-IP, deubiquitination assay, USP45/Coro1B knockout in Drosophila and mammalian cells, F-actin imaging, lysosomal V-ATPase localization, and N-WASP epistasis\",\n      \"pmids\": [\"40067150\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Ubiquitin ligase that opposes USP45 on CORO1B not identified\", \"Direct molecular link between CORO1B and F-actin patch suppression not fully defined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CORO1B simultaneously inhibits ARP2/3 yet promotes branched-actin turnover, and how its distinct roles across migration, junctions, secretion, and autophagy are coordinated, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No structural model of CORO1B bound to ARP2/3 or F-actin\", \"Unifying biochemical mechanism reconciling inhibition versus turnover-promotion absent\", \"Tissue-specific functional partitioning between coronin paralogs unclear\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1, 2, 6]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [3, 6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [3, 5, 6]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [2, 5]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"ARPC (ARP2/3 complex)\", \"ILK\", \"USP45\", \"PRKCE\", \"PARVA\", \"WASL\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}