CORO1B

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).

1. 1998 Medium

   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

   PMID:9778037

   Open questions at the time

   • No functional data beyond expression pattern
   • Actin-binding activity inferred from homology, not directly demonstrated
2. 1999 Medium

   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

   PMID:10574718

   Open questions at the time

   • No loss-of-function data
   • Specificity of antibody for CORO1B versus other coronins not fully resolved
3. 2007 High

   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

   PMID:17350576

   Open questions at the time

   • Structural basis of simultaneous Arp2/3 and SSH1L binding unknown
   • Whether Ser2 phosphorylation also regulates SSH1L recruitment was not resolved
4. 2008 High

   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

   PMID:18775315

   Open questions at the time

   • In vivo kinetics of debranching not measured
   • Contribution of other coronin family members to debranching not separated
5. 2011 High

   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

   PMID:21844203

   Open questions at the time

   • Single Coro1b−/− phenotype not independently characterized
   • Mechanism linking cortical actin to vesicle fusion not fully defined
6. 2012 High

   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

   PMID:22619279

   Open questions at the time

   • Whether other kinases also target Ser2 in different cell types is unknown
   • Downstream transcriptional consequences of CORO1B phosphorylation not addressed
7. 2013 Medium

   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

   PMID:23562652

   Open questions at the time

   • Other transcriptional regulators of CORO1B not identified
   • Whether CORO1B is required for cardiac EMT in vivo not tested by Coro1b knockout
8. 2020 Medium

   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

   PMID:32850828

   Open questions at the time

   • ILK interaction awaits reciprocal validation and domain mapping
   • In vivo vascular junction phenotype not tested
9. 2022 High

   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

   PMID:35657370

   Open questions at the time

   • Whether excess Cofilin in double KO reflects compensatory recruitment or trapping is unresolved
   • In vivo developmental phenotype of double knockout not reported
10. 2025 High

    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

    PMID:40067150

    Open questions at the time

    • Ubiquitin ligase(s) targeting CORO1B not identified
    • Whether autophagy activation upon CORO1B loss is physiologically relevant in specific tissues is unknown

• 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.
• 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