{"gene":"CORO1B","run_date":"2026-04-28T17:28:53","timeline":{"discoveries":[{"year":1998,"finding":"CORO1B (coronin-2) was identified as a member of a conserved family of four mouse coronin proteins (coronin-1, -2, -3, -4), all containing five highly conserved WD domains, with ubiquitous expression (unlike coronin-1 which is hematopoietic-restricted), and the gene for coronin-2 was localized to mouse chromosome 19, 5' of the CD45-associated protein gene.","method":"cDNA cloning, northern blot expression analysis, chromosomal mapping, sequence analysis of WD domains","journal":"DNA and cell biology","confidence":"Medium","confidence_rationale":"Tier 2 — original identification with direct molecular characterization, single lab","pmids":["9778037"],"is_preprint":false},{"year":1999,"finding":"Coronin-2 (CORO1B) was identified as an actin-binding protein associated with macrophage phagosomes, and a monoclonal antibody against it labeled phagosomes, cytoskeletal patterns, and plasma membrane in murine peritoneal macrophages.","method":"Monoclonal antibody screen, immunofluorescence, phagosome isolation and immunoblot","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 — direct localization by immunofluorescence with functional context of phagocytosis","pmids":["10574718"],"is_preprint":false},{"year":2007,"finding":"Coronin 1B simultaneously interacts with the Arp2/3 complex and Slingshot phosphatase (SSH1L); it inhibits actin filament nucleation by Arp2/3 complex, and this inhibition is attenuated by phosphorylation of Coronin 1B at Serine 2 (targeted by SSH1L). Coronin 1B directs SSH1L to lamellipodia where SSH1L dephosphorylates and activates Cofilin. Depletion of Coronin 1B increases phospho-Cofilin levels and alters lamellipodial dynamics and actin filament architecture at the leading edge.","method":"Co-immunoprecipitation, siRNA knockdown, in vitro actin assembly assays, phosphorylation site mutagenesis, live-cell imaging of lamellipodial dynamics","journal":"Cell","confidence":"High","confidence_rationale":"Tier 1–2 — multiple orthogonal methods including in vitro assays, mutagenesis, and live imaging; highly cited foundational paper","pmids":["17350576"],"is_preprint":false},{"year":2008,"finding":"Coronin 1B disassembles Arp2/3-containing actin filament branches by inducing Arp2/3 dissociation; this activity is antagonized by Cortactin (a filament branch stabilizer). Coronin 1B targets actin branches in a manner mutually exclusive with the Arp2/3 complex and alters the branch angle, replacing Arp2/3 at branches as the dendritic network matures to drive turnover of branched actin networks.","method":"In vitro reconstitution of actin branch disassembly, electron microscopy of branch angles, dual siRNA depletion epistasis, live-cell imaging","journal":"Cell","confidence":"High","confidence_rationale":"Tier 1 — reconstituted in vitro with EM validation, complemented by genetic epistasis; highly cited","pmids":["18775315"],"is_preprint":false},{"year":2011,"finding":"Coro1a and Coro1b exhibit functional dichotomy in mast cells: Coro1a knockout increases FcεRI-mediated degranulation of secretory lysosomes while reducing cytokine secretion; loss of both Coro1a and Coro1b further augments hyperdegranulation and enhanced passive cutaneous anaphylaxis in vivo. The inhibitory effect of Coro1a on degranulation requires its cortical localization, filamentous actin-binding activity, and is regulated by phosphorylation of Ser2.","method":"Genetic knockout (Coro1a−/−, Coro1a−/−Coro1b−/− mice), bone marrow-derived mast cell functional assays, in vivo passive cutaneous anaphylaxis, reconstitution assays with phosphorylation site mutants","journal":"The Journal of experimental medicine","confidence":"High","confidence_rationale":"Tier 2 — double knockout mice with in vivo and in vitro functional readouts, structure-function reconstitution","pmids":["21844203"],"is_preprint":false},{"year":2012,"finding":"Coronin 1B (Coro1B) is expressed in vascular smooth muscle cells (VSMCs) and its siRNA-mediated downregulation increases PDGF-induced migration by increasing lamellipodial protraction rate and protrusion distance. PDGF induces phosphorylation of Coro1B on Ser2 via PKCε, which decreases the interaction of Coro1B with the ARP2/3 complex; a phosphodeficient S2A mutant decreases PDGF-induced migration. Coro1B phosphorylation is increased in vivo after vessel injury in rat and mouse.","method":"siRNA knockdown, kymograph analysis of lamellipodia, co-immunoprecipitation (Coro1B-ARP2/3), phosphodeficient mutant transfection, in vivo vascular injury model with phospho-specific immunostaining","journal":"Circulation research","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP, phosphorylation site mutagenesis, in vivo validation; multiple orthogonal methods","pmids":["22619279"],"is_preprint":false},{"year":2013,"finding":"Coronin 1B is ubiquitously expressed during mouse development but shows distinct enrichment in endocardial cushion and epicardium during cardiac EMT. The Wilms' tumor suppressor Wt1 directly binds GC-rich sequences in the Coro1b promoter (between -1038 and -681) to regulate its transcription. Wt1 mutant embryos show decreased Coronin 1B expression in remaining epicardium, correlating with motility defects seen in Coro1b knockdown cells.","method":"Promoter deletion analysis, chromatin immunoprecipitation (ChIP), in situ hybridization/immunofluorescence, Wt1 knockout mouse analysis, siRNA knockdown motility assay","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2 — direct binding demonstrated by ChIP and promoter deletion with functional in vivo validation","pmids":["23562652"],"is_preprint":false},{"year":2015,"finding":"Arp2/3 complexes containing ARPC1B/ARPC5L are disassembled ~2-fold slower than those with ARPC1A/ARPC5, partly because cortactin stabilizes ARPC1B/ARPC5L-containing complexes against coronin-mediated disassembly, demonstrating that coronin (including Coro1B-related mechanisms) selectively disassembles specific Arp2/3 isoform complexes.","method":"In vitro reconstitution of branched actin networks, quantitative TIRF microscopy, biochemical disassembly assays with purified proteins","journal":"Nature cell biology","confidence":"Medium","confidence_rationale":"Tier 1 — in vitro reconstitution; specific attribution to CORO1B is partial (coronin family activity used)","pmids":["26655834"],"is_preprint":false},{"year":2020,"finding":"Coronin 1B (Coro1B) is a novel component of endothelial cell-cell junctions, colocalizing with VE-cadherin. Live-cell imaging shows Coro1B is recruited to actin-driven membrane protrusions at cell-cell junctions via a mechanism requiring relaxation of the actomyosin cytoskeleton. Interactome analysis identifies integrin-linked kinase (ILK) as a new Coro1B-associated protein; Coro1B colocalizes with α-parvin at lamellipodia leading edges. Depletion of Coro1B causes defects in actin cytoskeleton and cell-cell junctions and reduces endothelial network complexity in tube formation assays.","method":"Immunofluorescence, live-cell imaging, AP-MS interactome analysis (Coro1B pulldown), siRNA knockdown with Matrigel tube network assay","journal":"Frontiers in cell and developmental biology","confidence":"Medium","confidence_rationale":"Tier 2–3 — direct localization with functional consequence, AP-MS interactome, KD phenotype; single lab","pmids":["32850828"],"is_preprint":false},{"year":2022,"finding":"Conditional double knockout of Coro1B and Coro1C in cells shows these coronins strongly 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 in lamellipodia, causing excessive cofilin accumulation (inconsistent with simple pro-cofilin models), increased F-actin levels, defective haptotaxis, and increased cellular contractility.","method":"Conditional CRISPR knockout cell lines, live-cell fluorescence microscopy, F-actin quantification, haptotaxis assay, TIRF imaging of lamellipodia dynamics, traction force microscopy","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 — clean conditional double KO with multiple orthogonal phenotypic readouts, mechanistic pathway analysis","pmids":["35657370"],"is_preprint":false},{"year":2025,"finding":"CORO1B is a substrate of the deubiquitinase USP45: USP45 directly interacts with and deubiquitinates Coro1B, stabilizing its protein levels. Loss of USP45 or Coro1B promotes formation of F-actin patches and translocation of V-ATPase to lysosomes in an N-WASP-dependent manner, thereby activating autophagy and enhancing lysosomal acidification.","method":"Co-immunoprecipitation, deubiquitination assays, Drosophila and mammalian cell loss-of-function studies, immunofluorescence of F-actin and V-ATPase localization, autophagy flux assays","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1–2 — direct biochemical deubiquitination assay, orthologous validation in Drosophila and mammalian cells, functional consequence defined","pmids":["40067150"],"is_preprint":false}],"current_model":"CORO1B is a WD-repeat actin-binding protein that coordinates branched actin network turnover at lamellipodia by simultaneously inhibiting Arp2/3-mediated filament nucleation and directing Slingshot phosphatase (SSH1L) to dephosphorylate/activate Cofilin; its inhibitory interaction with Arp2/3 is relieved by PKCε-mediated phosphorylation at Ser2, promoting cell migration, and it is stabilized post-translationally by the deubiquitinase USP45, whose loss triggers N-WASP-dependent F-actin remodeling that promotes lysosomal V-ATPase recruitment and autophagy activation."},"narrative":{"teleology":[{"year":1998,"claim":"Identification of CORO1B as a ubiquitously expressed coronin family member established that coronin-type WD-repeat actin regulators are not restricted to hematopoietic cells, raising the question of what distinct cellular roles the broadly expressed paralog performs.","evidence":"cDNA cloning, northern blot, chromosomal mapping in mouse","pmids":["9778037"],"confidence":"Medium","gaps":["No functional data beyond expression pattern","Actin-binding activity inferred from homology, not directly demonstrated"]},{"year":1999,"claim":"Localization of CORO1B to phagosomes and cortical actin in macrophages provided the first evidence that this coronin paralog operates at actin-rich membrane structures, though its precise molecular function remained undefined.","evidence":"Monoclonal antibody immunofluorescence and phagosome proteomics in murine macrophages","pmids":["10574718"],"confidence":"Medium","gaps":["No loss-of-function data","Specificity of antibody for CORO1B versus other coronins not fully resolved"]},{"year":2007,"claim":"Demonstration that CORO1B simultaneously binds Arp2/3 (inhibiting nucleation) and recruits SSH1L to dephosphorylate Cofilin at lamellipodia resolved how a single protein coordinates both branch suppression and filament severing to drive actin network turnover.","evidence":"Co-IP, in vitro actin assembly, Ser2 mutagenesis, siRNA knockdown, and live-cell lamellipodial imaging in mammalian cells","pmids":["17350576"],"confidence":"High","gaps":["Structural basis of simultaneous Arp2/3 and SSH1L binding unknown","Whether Ser2 phosphorylation also regulates SSH1L recruitment was not resolved"]},{"year":2008,"claim":"Reconstitution of CORO1B-mediated Arp2/3 displacement from actin branches established a direct debranching mechanism antagonized by Cortactin, explaining how lamellipodial networks are remodeled as they mature.","evidence":"In vitro branch disassembly reconstitution, electron microscopy of branch angles, dual siRNA epistasis","pmids":["18775315"],"confidence":"High","gaps":["In vivo kinetics of debranching not measured","Contribution of other coronin family members to debranching not separated"]},{"year":2011,"claim":"Genetic knockout studies in mast cells revealed that CORO1B cooperates with CORO1A to restrict degranulation, demonstrating a physiological role for coronin-mediated actin regulation in regulated exocytosis and allergic responses.","evidence":"Coro1a−/− and Coro1a−/−Coro1b−/− bone marrow-derived mast cells, in vivo passive cutaneous anaphylaxis, Ser2 mutant reconstitution","pmids":["21844203"],"confidence":"High","gaps":["Single Coro1b−/− phenotype not independently characterized","Mechanism linking cortical actin to vesicle fusion not fully defined"]},{"year":2012,"claim":"Identification of PKCε as the kinase phosphorylating CORO1B Ser2 downstream of PDGF signaling in vascular smooth muscle cells connected growth factor signaling to Arp2/3 de-repression, explaining how CORO1B-mediated migration restraint is acutely relieved during vascular injury.","evidence":"Co-IP, phospho-specific antibodies, S2A mutagenesis, kymography, in vivo vascular injury model","pmids":["22619279"],"confidence":"High","gaps":["Whether other kinases also target Ser2 in different cell types is unknown","Downstream transcriptional consequences of CORO1B phosphorylation not addressed"]},{"year":2013,"claim":"Discovery that WT1 directly binds the CORO1B promoter to drive its expression during cardiac epithelial-to-mesenchymal transition linked CORO1B transcriptional regulation to developmental morphogenesis.","evidence":"ChIP, promoter deletion, in situ hybridization, Wt1 knockout embryos, siRNA motility assay","pmids":["23562652"],"confidence":"Medium","gaps":["Other transcriptional regulators of CORO1B not identified","Whether CORO1B is required for cardiac EMT in vivo not tested by Coro1b knockout"]},{"year":2020,"claim":"Localization of CORO1B to endothelial cell-cell junctions and identification of ILK as a binding partner expanded its functional repertoire beyond lamellipodia to junction-associated actin remodeling relevant to vascular integrity.","evidence":"Immunofluorescence, live-cell imaging, AP-MS interactome, siRNA knockdown with tube formation assay in endothelial cells","pmids":["32850828"],"confidence":"Medium","gaps":["ILK interaction awaits reciprocal validation and domain mapping","In vivo vascular junction phenotype not tested"]},{"year":2022,"claim":"Conditional double knockout of CORO1B and CORO1C established that these coronins are functionally redundant in limiting branched actin density, and revealed that their loss unexpectedly increases rather than decreases Cofilin accumulation at lamellipodia, revising the simple model of coronins as Cofilin activators.","evidence":"Conditional CRISPR knockout, TIRF imaging, F-actin quantification, haptotaxis assay, traction force microscopy","pmids":["35657370"],"confidence":"High","gaps":["Whether excess Cofilin in double KO reflects compensatory recruitment or trapping is unresolved","In vivo developmental phenotype of double knockout not reported"]},{"year":2025,"claim":"Identification of USP45 as the deubiquitinase that stabilizes CORO1B protein levels, and the finding that CORO1B loss triggers N-WASP-dependent F-actin patch formation driving V-ATPase lysosomal recruitment and autophagy, revealed an unexpected connection between actin network regulation and lysosomal function.","evidence":"Deubiquitination assays, Co-IP, Drosophila and mammalian loss-of-function, V-ATPase/lysosome imaging, autophagy flux assays","pmids":["40067150"],"confidence":"High","gaps":["Ubiquitin ligase(s) targeting CORO1B not identified","Whether autophagy activation upon CORO1B loss is physiologically relevant in specific tissues is unknown"]},{"year":null,"claim":"No structural model of CORO1B in complex with Arp2/3 or SSH1L exists, and the basis for simultaneous binding of these partners is unknown; additionally, the relative contributions of CORO1B versus CORO1C in vivo during development and tissue homeostasis remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No crystal or cryo-EM structure of CORO1B–Arp2/3 complex","Single Coro1b knockout mouse phenotype not comprehensively characterized","Tissue-specific functions beyond vascular and mast cell contexts largely unexplored"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[1,2,3,9]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[2,3,5,9]}],"localization":[{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[1,2,3,9]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[1,8]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[2,9]}],"pathway":[{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[10]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[2,5]}],"complexes":[],"partners":["ACTR2","ACTR3","SSH1","CTTN","CORO1C","USP45","ILK"],"other_free_text":[]},"mechanistic_narrative":"CORO1B is a WD-repeat-containing actin-binding protein that coordinates branched actin network turnover at lamellipodia and cell-cell junctions by simultaneously inhibiting Arp2/3-mediated filament nucleation and recruiting Slingshot phosphatase (SSH1L) to activate Cofilin-dependent filament disassembly [PMID:17350576, PMID:18775315, PMID:35657370]. Its inhibitory interaction with Arp2/3 is relieved by PKCε-mediated phosphorylation at Ser2, promoting lamellipodial dynamics and directed cell migration [PMID:22619279]. CORO1B functions redundantly with CORO1C to limit branched actin density and cellular contractility, and conditional loss of both coronins impairs haptotaxis and actin turnover [PMID:35657370]. CORO1B protein stability is maintained by USP45-mediated deubiquitination; loss of this stabilization triggers N-WASP-dependent F-actin remodeling that drives V-ATPase recruitment to lysosomes and autophagy activation [PMID:40067150]."},"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 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distinct carboxyl-terminal regions among family members.\",\n      \"method\": \"cDNA cloning, sequence analysis, expression profiling\",\n      \"journal\": \"DNA and cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — molecular characterization of domain architecture and expression pattern; single lab\",\n      \"pmids\": [\"9778037\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Coronin-2 (CORO1B) was identified as an actin-binding protein associated with macrophage phagosomes, localizing to phagosomes and displaying cytoskeletal staining patterns.\",\n      \"method\": \"Monoclonal antibody screen, immunofluorescence, immunoblot of purified phagosomes\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — antibody-based localization to phagosomes; single lab, single method\",\n      \"pmids\": [\"10574718\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Coro1b negatively regulates FcεRI-mediated mast cell degranulation; loss of Coro1b augments hyperdegranulation seen in Coro1a-null cells, and in vivo double-knockout mice show enhanced passive cutaneous anaphylaxis. The inhibitory effect of Coro1a on degranulation requires cortical localization, filamentous actin-binding activity, and is regulated by phosphorylation of Ser2.\",\n      \"method\": \"Genetic knockout (Coro1a−/−, Coro1a−/−Coro1b−/− mice), in vivo passive cutaneous anaphylaxis, functional reconstitution assays, mutagenesis (S2A Coro1a)\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — genetic epistasis with double KO, in vivo model, and reconstitution with mutagenesis\",\n      \"pmids\": [\"21844203\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"CORO1B is expressed in vascular smooth muscle cells (VSMCs) and negatively regulates PDGF-induced migration; siRNA knockdown of Coro1B increases lamellipodial protrusion rate and migration distance. PDGF induces phosphorylation of Coro1B on Ser-2 via PKCε, which disrupts its inhibitory interaction with the ARP2/3 complex. A phosphodeficient S2A Coro1B mutant decreases PDGF-induced migration. Coro1B phosphorylation is increased in vivo after vessel injury in rat and mouse.\",\n      \"method\": \"siRNA knockdown, kymograph analysis of lamellipodia, co-immunoprecipitation (Coro1B–ARP2/3), phosphodeficient mutagenesis (S2A), in vivo vascular injury model\",\n      \"journal\": \"Circulation research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods: KD phenotype, Co-IP, mutagenesis, in vivo validation\",\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 during cardiac development. Coro1b is expressed in endocardium, endocardial cushion, and epicardium where cardiac EMT processes occur. Wt1 mutant embryos show decreased Coro1B expression in epicardium, correlating with motility defects seen in Coro1b-knockdown cells.\",\n      \"method\": \"Promoter deletion analysis, chromatin immunoprecipitation (Wt1–Coro1b promoter), immunofluorescence in Wt1EGFPCre/EGFPCre mutant embryos, siRNA knockdown motility assay\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — promoter binding confirmed by ChIP, genetic mouse model, loss-of-function motility assay\",\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 via a mechanism requiring actomyosin relaxation. Coro1B is recruited to actin-driven membrane protrusions at junctions. Interactome analysis identified integrin-linked kinase (ILK) as a new Coro1B-associated protein, and Coro1B co-localizes with α-parvin at lamellipodia. Depletion of Coro1B causes defects in the actin cytoskeleton and cell-cell junctions, and reduces endothelial tube network complexity.\",\n      \"method\": \"Immunofluorescence, live-cell imaging, Coro1B interactome (mass spectrometry), Co-IP (Coro1B–ILK), siRNA knockdown, Matrigel tube assay\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple methods: live imaging, MS interactome, Co-IP, KD phenotype with defined readouts\",\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 their proper subcellular localization. Conditional double-knockout of Coro1B/Coro1C leads to increased branched actin density, reduced actin turnover, excessive cofilin accumulation in lamellipodia, defective lamellipodial protrusion dynamics, impaired haptotaxis, and increased cellular contractility.\",\n      \"method\": \"Conditional knockout cell lines, live-cell imaging, fluorescence microscopy, F-actin quantification, haptotaxis assay, contractility measurements\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — conditional KO with multiple orthogonal phenotypic readouts; mechanistic dissection of Arp2/3 dependence for localization\",\n      \"pmids\": [\"35657370\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"USP45 deubiquitinates and stabilizes Coro1B protein levels. Loss of USP45 or Coro1B promotes F-actin patch formation and translocation of V-ATPase to lysosomes in an N-WASP-dependent manner, thereby activating autophagy and enhancing lysosomal acidification.\",\n      \"method\": \"Co-immunoprecipitation (USP45–Coro1B), deubiquitination assay, genetic knockouts in Drosophila and mammalian cells, immunofluorescence, lysosomal acidification assay\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — biochemical deubiquitination assay, Co-IP, genetic KO in two organisms, mechanistic epistasis with N-WASP\",\n      \"pmids\": [\"40067150\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CORO1B is a WD-repeat actin-binding protein that inhibits Arp2/3-mediated branched actin assembly at lamellipodia, thereby suppressing cell migration and mast cell degranulation; phosphorylation of Ser-2 (by PKCε downstream of PDGF) relieves its inhibition of Arp2/3 to promote migration; it localizes to cell-cell junctions in endothelial cells via an actomyosin-relaxation-dependent mechanism and interacts with ILK; its abundance is controlled post-translationally by the deubiquitinase USP45, and Coro1B levels in turn regulate F-actin patch formation, V-ATPase lysosomal delivery, and autophagy flux in an N-WASP-dependent manner; transcriptionally, Coro1B expression is directly regulated by the Wt1 tumor suppressor in epicardial EMT.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1998,\n      \"finding\": \"CORO1B (coronin-2) was identified as a member of a conserved family of four mouse coronin proteins (coronin-1, -2, -3, -4), all containing five highly conserved WD domains, with ubiquitous expression (unlike coronin-1 which is hematopoietic-restricted), and the gene for coronin-2 was localized to mouse chromosome 19, 5' of the CD45-associated protein gene.\",\n      \"method\": \"cDNA cloning, northern blot expression analysis, chromosomal mapping, sequence analysis of WD domains\",\n      \"journal\": \"DNA and cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — original identification with direct molecular characterization, single lab\",\n      \"pmids\": [\"9778037\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Coronin-2 (CORO1B) was identified as an actin-binding protein associated with macrophage phagosomes, and a monoclonal antibody against it labeled phagosomes, cytoskeletal patterns, and plasma membrane in murine peritoneal macrophages.\",\n      \"method\": \"Monoclonal antibody screen, immunofluorescence, phagosome isolation and immunoblot\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct localization by immunofluorescence with functional context of phagocytosis\",\n      \"pmids\": [\"10574718\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Coronin 1B simultaneously interacts with the Arp2/3 complex and Slingshot phosphatase (SSH1L); it inhibits actin filament nucleation by Arp2/3 complex, and this inhibition is attenuated by phosphorylation of Coronin 1B at Serine 2 (targeted by SSH1L). Coronin 1B directs SSH1L to lamellipodia where SSH1L dephosphorylates and activates Cofilin. Depletion of Coronin 1B increases phospho-Cofilin levels and alters lamellipodial dynamics and actin filament architecture at the leading edge.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, in vitro actin assembly assays, phosphorylation site mutagenesis, live-cell imaging of lamellipodial dynamics\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — multiple orthogonal methods including in vitro assays, mutagenesis, and live imaging; highly cited foundational paper\",\n      \"pmids\": [\"17350576\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Coronin 1B disassembles Arp2/3-containing actin filament branches by inducing Arp2/3 dissociation; this activity is antagonized by Cortactin (a filament branch stabilizer). Coronin 1B targets actin branches in a manner mutually exclusive with the Arp2/3 complex and alters the branch angle, replacing Arp2/3 at branches as the dendritic network matures to drive turnover of branched actin networks.\",\n      \"method\": \"In vitro reconstitution of actin branch disassembly, electron microscopy of branch angles, dual siRNA depletion epistasis, live-cell imaging\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — reconstituted in vitro with EM validation, complemented by genetic epistasis; highly cited\",\n      \"pmids\": [\"18775315\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Coro1a and Coro1b exhibit functional dichotomy in mast cells: Coro1a knockout increases FcεRI-mediated degranulation of secretory lysosomes while reducing cytokine secretion; loss of both Coro1a and Coro1b further augments hyperdegranulation and enhanced passive cutaneous anaphylaxis in vivo. The inhibitory effect of Coro1a on degranulation requires its cortical localization, filamentous actin-binding activity, and is regulated by phosphorylation of Ser2.\",\n      \"method\": \"Genetic knockout (Coro1a−/−, Coro1a−/−Coro1b−/− mice), bone marrow-derived mast cell functional assays, in vivo passive cutaneous anaphylaxis, reconstitution assays with phosphorylation site mutants\",\n      \"journal\": \"The Journal of experimental medicine\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — double knockout mice with in vivo and in vitro functional readouts, structure-function reconstitution\",\n      \"pmids\": [\"21844203\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Coronin 1B (Coro1B) is expressed in vascular smooth muscle cells (VSMCs) and its siRNA-mediated downregulation increases PDGF-induced migration by increasing lamellipodial protraction rate and protrusion distance. PDGF induces phosphorylation of Coro1B on Ser2 via PKCε, which decreases the interaction of Coro1B with the ARP2/3 complex; a phosphodeficient S2A mutant decreases PDGF-induced migration. Coro1B phosphorylation is increased in vivo after vessel injury in rat and mouse.\",\n      \"method\": \"siRNA knockdown, kymograph analysis of lamellipodia, co-immunoprecipitation (Coro1B-ARP2/3), phosphodeficient mutant transfection, in vivo vascular injury model with phospho-specific immunostaining\",\n      \"journal\": \"Circulation research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP, phosphorylation site mutagenesis, in vivo validation; multiple orthogonal methods\",\n      \"pmids\": [\"22619279\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Coronin 1B is ubiquitously expressed during mouse development but shows distinct enrichment in endocardial cushion and epicardium during cardiac EMT. The Wilms' tumor suppressor Wt1 directly binds GC-rich sequences in the Coro1b promoter (between -1038 and -681) to regulate its transcription. Wt1 mutant embryos show decreased Coronin 1B expression in remaining epicardium, correlating with motility defects seen in Coro1b knockdown cells.\",\n      \"method\": \"Promoter deletion analysis, chromatin immunoprecipitation (ChIP), in situ hybridization/immunofluorescence, Wt1 knockout mouse analysis, siRNA knockdown motility assay\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct binding demonstrated by ChIP and promoter deletion with functional in vivo validation\",\n      \"pmids\": [\"23562652\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Arp2/3 complexes containing ARPC1B/ARPC5L are disassembled ~2-fold slower than those with ARPC1A/ARPC5, partly because cortactin stabilizes ARPC1B/ARPC5L-containing complexes against coronin-mediated disassembly, demonstrating that coronin (including Coro1B-related mechanisms) selectively disassembles specific Arp2/3 isoform complexes.\",\n      \"method\": \"In vitro reconstitution of branched actin networks, quantitative TIRF microscopy, biochemical disassembly assays with purified proteins\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 — in vitro reconstitution; specific attribution to CORO1B is partial (coronin family activity used)\",\n      \"pmids\": [\"26655834\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Coronin 1B (Coro1B) is a novel component of endothelial cell-cell junctions, colocalizing with VE-cadherin. Live-cell imaging shows Coro1B is recruited to actin-driven membrane protrusions at cell-cell junctions via a mechanism requiring relaxation of the actomyosin cytoskeleton. Interactome analysis identifies integrin-linked kinase (ILK) as a new Coro1B-associated protein; Coro1B colocalizes with α-parvin at lamellipodia leading edges. Depletion of Coro1B causes defects in actin cytoskeleton and cell-cell junctions and reduces endothelial network complexity in tube formation assays.\",\n      \"method\": \"Immunofluorescence, live-cell imaging, AP-MS interactome analysis (Coro1B pulldown), siRNA knockdown with Matrigel tube network assay\",\n      \"journal\": \"Frontiers in cell and developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 — direct localization with functional consequence, AP-MS interactome, KD phenotype; single lab\",\n      \"pmids\": [\"32850828\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Conditional double knockout of Coro1B and Coro1C in cells shows these coronins strongly 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 in lamellipodia, causing excessive cofilin accumulation (inconsistent with simple pro-cofilin models), increased F-actin levels, defective haptotaxis, and increased cellular contractility.\",\n      \"method\": \"Conditional CRISPR knockout cell lines, live-cell fluorescence microscopy, F-actin quantification, haptotaxis assay, TIRF imaging of lamellipodia dynamics, traction force microscopy\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean conditional double KO with multiple orthogonal phenotypic readouts, mechanistic pathway analysis\",\n      \"pmids\": [\"35657370\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"CORO1B is a substrate of the deubiquitinase USP45: USP45 directly interacts with and deubiquitinates Coro1B, stabilizing its protein levels. Loss of USP45 or Coro1B promotes formation of F-actin patches and translocation of V-ATPase to lysosomes in an N-WASP-dependent manner, thereby activating autophagy and enhancing lysosomal acidification.\",\n      \"method\": \"Co-immunoprecipitation, deubiquitination assays, Drosophila and mammalian cell loss-of-function studies, immunofluorescence of F-actin and V-ATPase localization, autophagy flux assays\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 — direct biochemical deubiquitination assay, orthologous validation in Drosophila and mammalian cells, functional consequence defined\",\n      \"pmids\": [\"40067150\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"CORO1B is a WD-repeat actin-binding protein that coordinates branched actin network turnover at lamellipodia by simultaneously inhibiting Arp2/3-mediated filament nucleation and directing Slingshot phosphatase (SSH1L) to dephosphorylate/activate Cofilin; its inhibitory interaction with Arp2/3 is relieved by PKCε-mediated phosphorylation at Ser2, promoting cell migration, and it is stabilized post-translationally by the deubiquitinase USP45, whose loss triggers N-WASP-dependent F-actin remodeling that promotes lysosomal V-ATPase recruitment and autophagy activation.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"CORO1B is a WD-repeat-containing actin-binding protein that functions as a negative regulator of Arp2/3-mediated branched actin assembly, thereby controlling lamellipodial dynamics, cell migration, and membrane trafficking. CORO1B co-localizes with Arp2/3-branched actin networks and inhibits the Arp2/3 complex; conditional double knockout of CORO1B and CORO1C increases branched actin density, reduces actin turnover, impairs haptotaxis, and elevates cellular contractility [PMID:35657370]. Phosphorylation of Ser-2 by PKCε downstream of PDGF signaling relieves CORO1B's inhibition of Arp2/3 to promote lamellipodial protrusion and vascular smooth muscle cell migration, while loss of CORO1B also augments mast cell degranulation and passive cutaneous anaphylaxis in vivo [PMID:22619279, PMID:21844203]. CORO1B protein abundance is controlled post-translationally by the deubiquitinase USP45, and reduction of CORO1B promotes N-WASP-dependent F-actin patch formation, V-ATPase delivery to lysosomes, and autophagy flux [PMID:40067150].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Identification of CORO1B as a conserved WD-repeat actin-binding protein established the existence of a coronin family with distinct isoforms, raising the question of isoform-specific functions.\",\n      \"evidence\": \"cDNA cloning and sequence/expression analysis in mice and humans\",\n      \"pmids\": [\"9778037\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional data beyond domain prediction and expression profiling\",\n        \"Actin-binding activity inferred from homology, not directly demonstrated for CORO1B\"\n      ]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Localization of CORO1B to macrophage phagosomes and the cytoskeleton provided the first evidence linking this isoform to actin-dependent membrane structures.\",\n      \"evidence\": \"Monoclonal antibody screen, immunofluorescence, and immunoblot of purified phagosomes\",\n      \"pmids\": [\"10574718\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single antibody-based approach without genetic validation\",\n        \"Functional role at phagosomes not tested\"\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Genetic evidence from double-knockout mice demonstrated that CORO1B cooperates with CORO1A to suppress mast cell degranulation, establishing CORO1B as a negative regulator of actin-dependent secretory events in immune cells.\",\n      \"evidence\": \"Coro1a−/−Coro1b−/− mice, passive cutaneous anaphylaxis in vivo, reconstitution with S2A mutant Coro1a\",\n      \"pmids\": [\"21844203\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Ser-2 phosphorylation was characterized on Coro1a in this study; equivalent regulation of Coro1b Ser-2 was not directly tested in mast cells\",\n        \"Identity of the kinase phosphorylating coronins in mast cells not determined\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"The mechanism by which CORO1B restrains cell migration was resolved: CORO1B inhibits the Arp2/3 complex, and PKCε-mediated Ser-2 phosphorylation downstream of PDGF disrupts this interaction, converting CORO1B from a brake to a permissive state for lamellipodial protrusion.\",\n      \"evidence\": \"siRNA knockdown with kymograph analysis, Co-IP of CORO1B–Arp2/3, S2A mutagenesis, in vivo vascular injury model in rat and mouse\",\n      \"pmids\": [\"22619279\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct structural basis for how Ser-2 phosphorylation disrupts Arp2/3 binding not resolved\",\n        \"Whether other kinases can phosphorylate Ser-2 in non-VSMC contexts remains untested\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Transcriptional regulation of CORO1B was connected to cardiac development: Wt1 directly binds the Coro1b promoter, and Wt1 loss reduces CORO1B in the epicardium, linking CORO1B to epithelial-to-mesenchymal transition during heart morphogenesis.\",\n      \"evidence\": \"Promoter deletion analysis, ChIP of Wt1 on Coro1b promoter, Wt1 mutant mouse embryos, siRNA knockdown motility assay\",\n      \"pmids\": [\"23562652\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether CORO1B is required for epicardial EMT in vivo (Coro1b cardiac-specific KO) not tested\",\n        \"Other transcription factors regulating CORO1B in non-cardiac contexts unknown\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"CORO1B was shown to localize to VE-cadherin junctions in endothelial cells and to interact with integrin-linked kinase (ILK), expanding its functional scope to endothelial junction maintenance and angiogenesis.\",\n      \"evidence\": \"Immunofluorescence, live-cell imaging, mass spectrometry interactome, Co-IP of CORO1B–ILK, siRNA knockdown, Matrigel tube assay\",\n      \"pmids\": [\"32850828\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Functional consequence of CORO1B–ILK interaction on junction integrity not mechanistically dissected\",\n        \"In vivo endothelial-specific knockout not performed\"\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Conditional double knockout of CORO1B and CORO1C definitively established that type I coronins limit branched actin density and promote actin network turnover in lamellipodia, with loss causing excessive cofilin accumulation and impaired haptotaxis.\",\n      \"evidence\": \"Conditional knockout cell lines, live-cell imaging, F-actin quantification, haptotaxis and contractility assays\",\n      \"pmids\": [\"35657370\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Individual contributions of CORO1B versus CORO1C not fully separated due to redundancy\",\n        \"Molecular mechanism by which coronins promote cofilin-mediated turnover not resolved\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The post-translational control of CORO1B abundance was identified: USP45 deubiquitinates and stabilizes CORO1B, and loss of CORO1B triggers N-WASP-dependent F-actin patch formation that drives V-ATPase to lysosomes, activating autophagy.\",\n      \"evidence\": \"Co-IP and deubiquitination assay (USP45–CORO1B), genetic knockouts in Drosophila and mammalian cells, lysosomal acidification assay\",\n      \"pmids\": [\"40067150\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Specific ubiquitin chain type and E3 ligase targeting CORO1B for degradation not identified\",\n        \"Whether USP45-CORO1B axis regulates autophagy in vivo in mammalian tissues not tested\",\n        \"Mechanism linking F-actin patches to V-ATPase translocation remains unclear\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key open questions include the structural basis of Ser-2 phosphorylation-dependent release of Arp2/3, the E3 ligase opposing USP45, the individual versus redundant contributions of CORO1B and CORO1C in vivo, and whether the autophagy-regulatory function operates in physiological contexts such as immune cells or the vasculature.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No structural model of CORO1B–Arp2/3 interface\",\n        \"E3 ubiquitin ligase targeting CORO1B unknown\",\n        \"In vivo phenotype of single Coro1b knockout in most tissues not characterized\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1, 3, 6]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [3, 6, 7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [1, 3, 6]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [2, 5]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [5, 6]},\n      {\"term_id\": \"GO:0005764\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [3]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"ACTR2\",\n      \"ACTR3\",\n      \"ILK\",\n      \"USP45\",\n      \"CORO1A\",\n      \"CORO1C\",\n      \"WT1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"CORO1B is a WD-repeat-containing actin-binding protein that coordinates branched actin network turnover at lamellipodia and cell-cell junctions by simultaneously inhibiting Arp2/3-mediated filament nucleation and recruiting Slingshot phosphatase (SSH1L) to activate Cofilin-dependent filament disassembly [PMID:17350576, PMID:18775315, PMID:35657370]. Its inhibitory interaction with Arp2/3 is relieved by PKCε-mediated phosphorylation at Ser2, promoting lamellipodial dynamics and directed cell migration [PMID:22619279]. CORO1B functions redundantly with CORO1C to limit branched actin density and cellular contractility, and conditional loss of both coronins impairs haptotaxis and actin turnover [PMID:35657370]. CORO1B protein stability is maintained by USP45-mediated deubiquitination; loss of this stabilization triggers N-WASP-dependent F-actin remodeling that drives V-ATPase recruitment to lysosomes and autophagy activation [PMID:40067150].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Identification of CORO1B as a ubiquitously expressed coronin family member established that coronin-type WD-repeat actin regulators are not restricted to hematopoietic cells, raising the question of what distinct cellular roles the broadly expressed paralog performs.\",\n      \"evidence\": \"cDNA cloning, northern blot, chromosomal mapping in mouse\",\n      \"pmids\": [\"9778037\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No functional data beyond expression pattern\", \"Actin-binding activity inferred from homology, not directly demonstrated\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Localization of CORO1B to phagosomes and cortical actin in macrophages provided the first evidence that this coronin paralog operates at actin-rich membrane structures, though its precise molecular function remained undefined.\",\n      \"evidence\": \"Monoclonal antibody immunofluorescence and phagosome proteomics in murine macrophages\",\n      \"pmids\": [\"10574718\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No loss-of-function data\", \"Specificity of antibody for CORO1B versus other coronins not fully resolved\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Demonstration that CORO1B simultaneously binds Arp2/3 (inhibiting nucleation) and recruits SSH1L to dephosphorylate Cofilin at lamellipodia resolved how a single protein coordinates both branch suppression and filament severing to drive actin network turnover.\",\n      \"evidence\": \"Co-IP, in vitro actin assembly, Ser2 mutagenesis, siRNA knockdown, and live-cell lamellipodial imaging in mammalian cells\",\n      \"pmids\": [\"17350576\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of simultaneous Arp2/3 and SSH1L binding unknown\", \"Whether Ser2 phosphorylation also regulates SSH1L recruitment was not resolved\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Reconstitution of CORO1B-mediated Arp2/3 displacement from actin branches established a direct debranching mechanism antagonized by Cortactin, explaining how lamellipodial networks are remodeled as they mature.\",\n      \"evidence\": \"In vitro branch disassembly reconstitution, electron microscopy of branch angles, dual siRNA epistasis\",\n      \"pmids\": [\"18775315\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo kinetics of debranching not measured\", \"Contribution of other coronin family members to debranching not separated\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Genetic knockout studies in mast cells revealed that CORO1B cooperates with CORO1A to restrict degranulation, demonstrating a physiological role for coronin-mediated actin regulation in regulated exocytosis and allergic responses.\",\n      \"evidence\": \"Coro1a−/− and Coro1a−/−Coro1b−/− bone marrow-derived mast cells, in vivo passive cutaneous anaphylaxis, Ser2 mutant reconstitution\",\n      \"pmids\": [\"21844203\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Single Coro1b−/− phenotype not independently characterized\", \"Mechanism linking cortical actin to vesicle fusion not fully defined\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Identification of PKCε as the kinase phosphorylating CORO1B Ser2 downstream of PDGF signaling in vascular smooth muscle cells connected growth factor signaling to Arp2/3 de-repression, explaining how CORO1B-mediated migration restraint is acutely relieved during vascular injury.\",\n      \"evidence\": \"Co-IP, phospho-specific antibodies, S2A mutagenesis, kymography, in vivo vascular injury model\",\n      \"pmids\": [\"22619279\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether other kinases also target Ser2 in different cell types is unknown\", \"Downstream transcriptional consequences of CORO1B phosphorylation not addressed\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Discovery that WT1 directly binds the CORO1B promoter to drive its expression during cardiac epithelial-to-mesenchymal transition linked CORO1B transcriptional regulation to developmental morphogenesis.\",\n      \"evidence\": \"ChIP, promoter deletion, in situ hybridization, Wt1 knockout embryos, siRNA motility assay\",\n      \"pmids\": [\"23562652\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Other transcriptional regulators of CORO1B not identified\", \"Whether CORO1B is required for cardiac EMT in vivo not tested by Coro1b knockout\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Localization of CORO1B to endothelial cell-cell junctions and identification of ILK as a binding partner expanded its functional repertoire beyond lamellipodia to junction-associated actin remodeling relevant to vascular integrity.\",\n      \"evidence\": \"Immunofluorescence, live-cell imaging, AP-MS interactome, siRNA knockdown with tube formation assay in endothelial cells\",\n      \"pmids\": [\"32850828\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"ILK interaction awaits reciprocal validation and domain mapping\", \"In vivo vascular junction phenotype not tested\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Conditional double knockout of CORO1B and CORO1C established that these coronins are functionally redundant in limiting branched actin density, and revealed that their loss unexpectedly increases rather than decreases Cofilin accumulation at lamellipodia, revising the simple model of coronins as Cofilin activators.\",\n      \"evidence\": \"Conditional CRISPR knockout, TIRF imaging, F-actin quantification, haptotaxis assay, traction force microscopy\",\n      \"pmids\": [\"35657370\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether excess Cofilin in double KO reflects compensatory recruitment or trapping is unresolved\", \"In vivo developmental phenotype of double knockout not reported\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identification of USP45 as the deubiquitinase that stabilizes CORO1B protein levels, and the finding that CORO1B loss triggers N-WASP-dependent F-actin patch formation driving V-ATPase lysosomal recruitment and autophagy, revealed an unexpected connection between actin network regulation and lysosomal function.\",\n      \"evidence\": \"Deubiquitination assays, Co-IP, Drosophila and mammalian loss-of-function, V-ATPase/lysosome imaging, autophagy flux assays\",\n      \"pmids\": [\"40067150\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Ubiquitin ligase(s) targeting CORO1B not identified\", \"Whether autophagy activation upon CORO1B loss is physiologically relevant in specific tissues is unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"No structural model of CORO1B in complex with Arp2/3 or SSH1L exists, and the basis for simultaneous binding of these partners is unknown; additionally, the relative contributions of CORO1B versus CORO1C in vivo during development and tissue homeostasis remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No crystal or cryo-EM structure of CORO1B–Arp2/3 complex\", \"Single Coro1b knockout mouse phenotype not comprehensively characterized\", \"Tissue-specific functions beyond vascular and mast cell contexts largely unexplored\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [1, 2, 3, 9]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [2, 3, 5, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [1, 2, 3, 9]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1, 8]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [2, 9]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [10]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [2, 5]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"ACTR2\",\n      \"ACTR3\",\n      \"SSH1\",\n      \"CTTN\",\n      \"CORO1C\",\n      \"USP45\",\n      \"ILK\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}