Directed Actin Polymerization Is the Driving Force for Epithelial Cell–Cell Adhesion
Open accessAbstract
We have found that epithelial cells engage in a process of cadherin-mediated intercellular adhesion that utilizes calcium and actin polymerization in unexpected ways. Calcium stimulates filopodia, which penetrate and embed into neighboring cells. E-cadherin complexes cluster at filopodia tips, generating a two-rowed zipper of embedded puncta. Opposing cell surfaces are clamped by desmosomes, while vinculin, zyxin, VASP, and Mena are recruited to adhesion zippers by a mechanism that requires alpha-catenin. Actin reorganizes and polymerizes to merge puncta into a single row and seal cell borders. In keratinocytes either null for alpha-catenin or blocked in VASP/Mena function, filopodia embed, but actin reorganization/polymerization is prevented, and membranes cannot seal. Taken together, a dynamic mechanism for intercellular adhesion is unveiled involving calcium-activated filopodia penetration and VASP/Mena-dependent actin reorganization/polymerization.
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Control keratinocytes form regularly spaced cadherin-catenin-complex-positive early intercellular junctions (zippers) that recruit vinculin, F-actin and ZO-1.
“Control cells formed regularly spaced cadherin-catenin-complex-positive early intercellular junctions, also known as zippers21, which recruit both vinculin, F-actin and ZO-1 (Fig. 5a–c; Supplementary Fig. 5a).”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [21]
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- Authors
- Vasioukhin, V., Bauer, C., Yin, M., & Fuchs, E.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Fuchs, Elaine
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2000-01
- Volume
- 100
- Issue
- 2
- Pages
- 209-219
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2058416613
- Cited by
- 1,205
- References
- 0
- Citations by year
- 2026: 23 · 2025: 28 · 2024: 26 · 2023: 26 · 2022: 24 · 2021: 28 · 2020: 29 · 2019: 27 · 2018: 39 · 2017: 47 · 2016: 29 · 2015: 45 · 2014: 51 · 2013: 47 · 2012: 71
- FWCI
- 25.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR027883, R01 AR27883)
- National Institute of Dental and Craniofacial Research (5P50DE11921, P50DE011921)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- cadherin-mediated adhesion, E-cadherin, actin polymerization, filopodia, calcium signaling, alpha-catenin, VASP, Middle East and North Africa, desmosomes, keratinocytes, membrane sealing, zyxin, vinculin
- MeSH terms
- Vasodilator-Stimulated Phosphoprotein, Actins, Animals, Animals, Newborn, Calcium, Carrier Proteins, Cell Adhesion, Cells, Cultured, Cytoskeletal Proteins, Fluorescent Antibody Technique, Intercellular Junctions, Metalloproteins, Microfilament Proteins, Phosphoproteins, Polymers, Pseudopodia, Stress, Mechanical, Keratinocytes, Cell Adhesion Molecules, Cadherins, Microscopy, Immunoelectron, Vinculin, Mice, Knockout, alpha Catenin, Mice, Zyxin, In Vitro Techniques
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