ArticleScience advances2025
Afadin mediates cadherin-catenin complex clustering on F-actin linked to cooperative binding and filament curvature.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Article
- F-actin organization excludes E-cadherin from the division furrow to ensure cytokinesis fidelity.Life science alliance · 2026Article
- Two δ-catenins, plakophilin 4 and p120, promote formation of distinct types of adherens junctions.The Journal of cell biology · 2026Article
- Review
- Microtubules guide Aurora B substrate geometries for accurate chromosome segregation.Science advances · 2026Article
- Intact Mass Profiling Reveals Phospho-Proteoforms of the Catenins (85-110 kDa) Regulated by Actomyosin Contractility.Angewandte Chemie (International ed. in English) · 2025Article
- A key role of Canoe's intrinsically disordered region in linking cell junctions to the cytoskeleton.The Journal of cell biology · 2025Article
- Paths to stability - actin regulation of adherens junction mechanics.Journal of cell science · 2025Review
- Distinct strategies of epithelial cell barrier disruption by Leptospira interrogans isolated from human patients in Okinawa, Japan.PLoS neglected tropical diseases · 2025Article
- PAK4 promotes vertex remodeling to maintain epithelial integrity and barrier function.bioRxiv : the preprint server for biology · 2025Article
- E-Cadherin: A conductor of cellular signaling.Current opinion in cell biology · 2025Review
- Proximity proteomics provides a new resource for exploring the function of Afadin and the complexity of cell-cell adherens junctions.Biology open · 2025Article
- Proximity proteomics provides a new resource for exploring the function of Afadin and the complexity of cell-cell adherens junctions.bioRxiv : the preprint server for biology · 2024Article
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4 authors.
Funding
Abstract
The E-cadherin-β-catenin-αE-catenin (cadherin-catenin) complex couples the cytoskeletons of neighboring cells at adherens junctions (AJs) to mediate force transmission across epithelia. Mechanical force and auxiliary binding partners converge to stabilize the cadherin-catenin complex's inherently weak binding to actin filaments (F-actin) through unclear mechanisms. Here, we show that afadin's coiled-coil (CC) domain and vinculin synergistically enhance the cadherin-catenin complex's F-actin engagement. The cryo-electron microscopy (cryo-EM) structure of an E-cadherin-β-catenin-αE-catenin-vinculin-afadin-CC supra-complex bound to F-actin reveals that afadin-CC bridges adjacent αE-catenin actin-binding domains along the filament, stabilizing flexible αE-catenin segments implicated in mechanical regulation. These cooperative binding contacts promote the formation of supra-complex clusters along F-actin. Additionally, cryo-EM variability analysis links supra-complex binding along individual F-actin strands to nanoscale filament curvature, a deformation mode associated with cytoskeletal forces. Collectively, this work elucidates a mechanistic framework by which vinculin and afadin tune cadherin-catenin complex-cytoskeleton coupling to support AJ function across varying mechanical regimes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.