| 2011 |
Cobl forms complexes with syndapin I in vivo (coimmunoprecipitation, colocalization, subcellular recruitment). Syndapin I recruits Cobl to membranes via its F-BAR domain (in vitro reconstitution and subcellular fractionation). Syndapin I RNAi impairs cortical localization of Cobl. Cobl, syndapin I, and N-WASP co-exist in one complex. Cobl-mediated functions in neuronal morphogenesis (dendritic arbor development) critically rely on syndapin I and on Arp3. |
Coimmunoprecipitation, colocalization, subcellular fractionation, in vitro reconstitution, RNAi knockdown with neuronal morphology readout |
The EMBO journal |
High |
21725280
|
| 2012 |
Cobl plays a crucial role in Purkinje cell dendritic arborization (branch point number, density, and higher-order branching). Cobl physically associates with the F-actin-binding protein Abp1 (subcellular fractionation, protein interaction analysis, reconstitution, colocalization). Cobl-mediated dendritic branch induction critically relies on Abp1, and a Cobl mutant deficient for Abp1 binding fails to rescue Cobl loss-of-function phenotypes. Abp1-mediated F-actin association is required for Cobl function, as an Abp1 mutant supporting Cobl association but lacking F-actin binding also failed to rescue. |
Gene gun transfection in cerebellar slices, RNAi knockdown, subcellular fractionation, protein interaction/co-IP, subcellular reconstitution, colocalization, functional rescue with point mutants |
The Journal of neuroscience |
High |
23223303
|
| 2012 |
In zebrafish, Cobl and syndapin I colocalize at the base of forming cilia and are both required for formation of kinocilia and F-actin-rich stereocilia in lateral line sensory hair cells. Proper formation of ciliated sensory hair cell rosettes requires Cobl's syndapin I-binding Cobl homology domain and the actin-nucleating C-terminus of Cobl. Loss of Cobl or syndapin I causes similar lateral line defects, supporting they function together. |
Morpholino knockdown in zebrafish, scanning electron microscopy, colocalization, rescue experiments with domain mutants |
Journal of cell science |
High |
23203810
|
| 2015 |
Cobl actin nucleation activity requires all three of its WH2 domains. Cobl is directly regulated by Ca2+/calmodulin (CaM): Ca2+/CaM modulates Cobl's actin-binding properties and promotes Cobl's interactions with syndapin I. CaM inhibitor studies showed Cobl-mediated dendritic branching is strictly dependent on CaM activity. Cobl-induced dendritic branch initiation was preceded by Ca2+ signals and coincided with local F-actin and CaM accumulations. CaM-binding-defective Cobl mutants failed to rescue Cobl loss-of-function phenotypes. |
Overexpression and rescue experiments in primary neurons and tissue slices, CaM inhibitor studies, Ca2+ imaging, in vitro actin binding/nucleation assays, mutagenesis of CaM-binding sites |
PLoS biology |
High |
26334624
|
| 2018 |
Cobl is controlled by arginine methylation via PRMT2. PRMT2 associates with Cobl in an SH3 domain-dependent manner (coprecipitation, Co-IP, cellular and in vitro reconstitutions), and this promotes methylation of Cobl's actin-nucleating C-terminal domain. Cobl methylation is key for Cobl actin binding. PRMT2 phenocopies Cobl in gain- and loss-of-function dendritogenesis assays. Cobl-mediated dendritic arborization required complex formation with PRMT2 and PRMT2's catalytic activity. |
Coprecipitation, coimmunoprecipitation, cellular and in vitro reconstitution, gain- and loss-of-function in neurons, catalytic mutant of PRMT2, actin binding assays |
Developmental cell |
High |
29689199
|
| 2018 |
Cobl is required for postnatal planar cell polarity refinement in cochlear hair cells. Cobl KO mice show reduced F-actin beneath the sensory apparatus, premature kinocilium retraction, and mispositioned basal bodies/centrioles during the critical period of hearing onset. Pericentriolar scaffold defects in Cobl KO mice are actin polymerization-dependent and Ca2+/calmodulin signaling-dependent. |
Cobl KO mouse analysis, F-actin staining, centriole/basal body positioning imaging, Ca2+/CaM inhibitor treatment, actin polymerization inhibitor treatment |
Cell reports |
High |
30157434
|
| 2020 |
COBL physically interacts with and is stabilized by IGFN1 in skeletal muscle. COBL localizes to the Z-disc in adult muscle. IGFN1 interaction prevents COBL's ability to form actin ruffles in COS7 cells. COBL is expressed in differentiating C2C12 myoblasts but not in proliferating cells. COBL loss-of-function C2C12 clones are able to fuse, indicating COBL is not essential for myoblast fusion. |
Pulldown with IGFN1 fragments followed by proteomics, co-IP validation, colocalization imaging, COS7 cell actin ruffle assay, COBL KO C2C12 clones |
Experimental cell research |
Medium |
32768501
|
| 2021 |
Cobl and Cobl-like act interdependently in dendritic arbor development; neither alone is sufficient. Syndapin I physically links Cobl and Cobl-like by forming nanodomains at convex plasma membrane areas at protrusion bases and interacting with three motifs in Cobl-like, one of which is Ca2+/calmodulin-regulated. Cobl-like's N-terminal calmodulin-binding site and Ca2+/CaM-responsive syndapin-binding motif are both critical for Cobl-like's dendritogenic function. |
Co-IP, colocalization, TIRF/superresolution imaging of syndapin nanodomains, loss-of-function and rescue experiments with domain/point mutants in neurons |
eLife |
High |
34264190
|
| 2021 |
Cobl is required for poststroke dendritic arbor repair in peri-infarct penumbral neurons. Ischemic stroke and excitotoxicity cause calpain-mediated proteolysis of Cobl, significantly reducing Cobl levels. Cobl levels are subsequently restored by increased mRNA expression. In Cobl KO mice, the dendritic repair window (day 2-4 post-stroke) passed without dendritic regrowth, demonstrating Cobl is causally required for poststroke recovery. |
Mouse MCAO model, Cobl KO mice, dendritic morphometry, calpain inhibitor treatment, mRNA quantification |
PLoS biology |
High |
34898601
|
| 2025 |
Cobl is expressed in ameloblasts during amelogenesis, particularly during the secretory phase, and colocalizes with actin filaments at the cell cortex. Cobl KO causes increased ameloblast height, increased apical F-actin at P0, and reduced apical F-actin density during maturation phase. Cobl-deficient mice show altered enamel composition (increased carbon content) and increased enamel surface area, demonstrating Cobl's role in actin cytoskeletal organization during enamel formation. |
Cobl KO mouse analysis, immunofluorescence colocalization, F-actin density quantification, enamel composition analysis |
Cells |
Medium |
40072087
|
| 2025 |
Cobl KO mice lack a transient cortical dendritic arbor expansion that occurs during emerging adulthood (in layer V during adolescence and layer II/III during emerging adulthood in somatosensory, prefrontal, and motor cortex). This expansion is accompanied by transient dendritic spine length changes, linking the process to actin dynamics. Cobl is thus the first molecular component identified as required for emerging adulthood-related neuronal arbor changes during brain maturation. |
Cobl KO mouse, dendritic morphometry at multiple developmental time points across cortical layers |
The Journal of neuroscience |
Medium |
40555515
|