Cadherin Adhesion and Mechanotransduction
Open accessAbstract
Cadherins are the principal adhesion proteins at intercellular junctions and function as the biochemical Velcro that binds cells together. Besides this mechanical function, cadherin complexes are also mechanotransducers that sense changes in tension and trigger adaptive reinforcement of intercellular junctions. The assembly and regulation of cadherin adhesions are central to their mechanical functions, and new evidence is presented for a comprehensive model of cadherin adhesion, which is surprisingly more complex than previously appreciated. Recent findings also shed new light on mechanisms that regulate cadherin junction assembly, adhesion, and mechanotransduction. We further describe recent evidence for cadherin-based mechanotransduction, and the rudiments of the molecular mechanism, which involves α-catenin and vinculin as key elements. Potential roles of a broader cast of possible force-sensitive partners are considered, as well as known and speculative biological consequences of adhesion and force transduction at cadherin-mediated junctions.
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Increased tension across junctions results in the unfolding of α-catenin, exposing a binding site for vinculin, which then reinforces interactions with the actomyosin cytoskeleton.
“On a molecular level, increased tension across junctions results in the unfolding of α-catenin, exposing a binding site for vinculin, which then reinforces interactions with the actomyosin cytoskeleton7, 8.”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [8]
The sections “α-Catenin Is a Central Molecule in Cadherin Mechanotransduction” and “Vinculin Is a Key Effector of α-Catenin Mechanosensing” describe tension-dependent α-catenin opening, exposure of a vinculin-binding site, and vinculin recruitment to stressed junctions. The Figure 4 discussion says vinculin stabilizes junctions but explicitly states that how it does so is unclear; reinforcement through its interaction with F-actin is presented as a possibility, not an established mechanism. Page numbers are unavailable in our copy. (LLM, conf=0.87)
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- Authors
- Leckband, D. E., & de Rooij, J.
- Affiliations
- University of Illinois Urbana-Champaign (US)
- Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands;
- ORCID
- Leckband, D.E.
- Venue
- Annual Review of Cell and Developmental Biology
- Publisher
- Annual Reviews
- Published
- 2014-10-11
- Volume
- 30
- Issue
- 1
- Pages
- 291-315
- ISSN
- 1081-0706 (ISSN-L)
- 1530-8995
- OpenAlex
- W2132375258
- Cited by
- 394
- References
- 7
- Citations by year
- 2026: 14 · 2025: 25 · 2024: 32 · 2023: 28 · 2022: 34 · 2021: 55 · 2020: 35 · 2019: 35 · 2018: 37 · 2017: 41 · 2016: 28 · 2015: 20 · 2014: 10
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Cell and Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (1132116)
- National Institutes of Health
- National Institute of General Medical Sciences (R01 GM09743, R01GM097443)
- Division of Chemical, Bioengineering, Environmental, and Transport Systems
- Division of Civil, Mechanical and Manufacturing Innovation
- 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
- cadherins, cell adhesion, mechanotransduction, intercellular junctions, alpha-catenin, vinculin, force transduction
- MeSH terms
- Actins, Allosteric Regulation, Animals, Cell Adhesion, Cytoskeleton, Endocytosis, Glycosylation, Humans, Models, Biological, Models, Molecular, Morphogenesis, Protein Processing, Post-Translational, Structure-Activity Relationship, Signal Transduction, Cadherins, Vinculin, Protein Structure, Tertiary, Mechanotransduction, Cellular, alpha Catenin
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