CORO1B

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).

1. 1998 Medium

   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

   PMID:9778037

   Open questions at the time

   • No functional assay tying the domains to a specific actin activity
   • Ubiquitous expression does not localize function to any pathway
2. 1999 Medium

   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

   PMID:10574718

   Open questions at the time

   • Localization only, no loss-of-function phenotype
   • Mechanism of phagosomal recruitment unknown
3. 2011 High

   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

   PMID:21844203

   Open questions at the time

   • 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
4. 2012 High

   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

   PMID:22619279

   Open questions at the time

   • Structural basis of the CORO1B–ARP2/3 interaction not resolved
   • Whether Ser-2 phosphorylation governs CORO1B function outside VSMCs unknown
5. 2013 Medium

   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

   PMID:23562652

   Open questions at the time

   • Functional consequence of WT1-driven Coro1b expression for epicardial biology not tested
   • Other transcriptional inputs not assessed
6. 2020 Medium

   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

   PMID:32850828

   Open questions at the time

   • Whether the ILK interaction is direct and functionally required not established
   • Recruitment mechanism via actomyosin relaxation not mechanistically dissected
7. 2022 High

   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

   PMID:35657370

   Open questions at the time

   • Mechanism reconciling cofilin accumulation with reduced turnover unresolved
   • Relative contributions of CORO1B versus CORO1C not separated
8. 2025 High

   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

   PMID:40067150

   Open questions at the time

   • Ubiquitin ligase that opposes USP45 on CORO1B not identified
   • Direct molecular link between CORO1B and F-actin patch suppression not fully defined

• 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.
• 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