Cited by 170Cell Adhesion Molecules ResearchCellular Mechanics and InteractionsConnexins and lens biology

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Calcium-dependent dynamics of cadherin interactions at cell–cell junctions

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Kim, Sally A., Tai, Chin-Yin, Mok, Lee-Peng, Mosser, Eric A., Schuman, Erin M.·2011·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1019003108PMC PMC3116393

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Abstract

Cadherins play a key role in the dynamics of cell–cell contact formation and remodeling of junctions and tissues. Cadherin–cadherin interactions are gated by extracellular Ca 2+ , which serves to rigidify the cadherin extracellular domains and promote trans junctional interactions. Here we describe the direct visualization and quantification of spatiotemporal dynamics of N -cadherin interactions across intercellular junctions in living cells using a genetically encodable FRET reporter system. Direct measurements of transjunctional cadherin interactions revealed a sudden, but partial, loss of homophilic interactions (τ = 1.17 ± 0.06 s −1 ) upon chelation of extracellular Ca 2+ . A cadherin mutant with reduced adhesive activity (W2A) exhibited a faster, more substantial loss of homophilic interactions (τ = 0.86 ± 0.02 s −1 ), suggesting two types of native cadherin interactions—one that is rapidly modulated by changes in extracellular Ca 2+ and another with relatively stable adhesive activity that is Ca 2+ independent. The Ca 2+ -sensitive dynamics of cadherin interactions were transmitted to the cell interior where β-catenin translocated to N -cadherin at the junction in both cells. These data indicate that cadherins can rapidly convey dynamic information about the extracellular environment to both cells that comprise a junction.

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“Cadherins regulate calcium-dependent cell–cell adherent junctions, where the chelation of calcium abolishes adhesive activity and allows proteolytic degradation of cadherins (Nagar and Overduint, 1996; Kim et al., 2011).”
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Authors: Kim, S. A., Tai, C.-Y., Mok, L.-P., Mosser, E. A., & Schuman, E. M.
Affiliations: California Institute of Technology (US)
ORCID: Kim, Sally A.
Tai, Chin-Yin
Schuman, Erin M.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2011-05-25
Volume: 108
Issue: 24
Pages: 9857-9862
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1019003108
PMC: PMC3116393
OpenAlex: W2071583976
Cited by: 170
References: 45
Citations by year: 2026: 13 · 2025: 9 · 2024: 22 · 2023: 17 · 2022: 17 · 2021: 10 · 2020: 15 · 2019: 13 · 2018: 7 · 2017: 8 · 2016: 10 · 2015: 10 · 2014: 9 · 2013: 7 · 2012: 3
FWCI: 4.52
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
CaltechAUTHORS (California Institute of Technology) (submittedVersion)
MPG.PuRe (Max Planck Society) (submittedVersion)
Funders: Howard Hughes Medical Institute
Topics: Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
Keywords: cadherins, N-cadherin, homophilic interactions, calcium signaling, cell-cell contact, FRET reporter, β-catenin nuclear translocation, cell adhesion, junction remodeling
MeSH terms: Animals, Calcium, Chlorocebus aethiops, Humans, Intercellular Junctions, Kinetics, L Cells, Protein Binding, Recombinant Fusion Proteins, Transfection, Cadherins, Microscopy, Confocal, COS Cells, Fluorescence Resonance Energy Transfer, Green Fluorescent Proteins, beta Catenin, Mice, HEK293 Cells

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Calcium-dependent dynamics of cadherin interactions at cell–cell junctions

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