Spatio-Temporal Regulation of Rac1 Localization and Lamellipodia Dynamics during Epithelial Cell-Cell Adhesion
Open accessAbstract
Cadherin-dependent epithelial cell-cell adhesion is thought to be regulated by Rho family small GTPases and PI 3-kinase, but the mechanisms involved are poorly understood. Using time-lapse microscopy and quantitative image analysis, we show that cell-cell contact in MDCK epithelial cells coincides with a spatio-temporal reorganization of plasma membrane Rac1 and lamellipodia from noncontacting to contacting surfaces. Within contacts, Rac1 and lamellipodia transiently concentrate at newest sites, but decrease at older, stabilized sites. Significantly, Rac1 mutants alter kinetics of cell-cell adhesion and strengthening, but not the eventual generation of cell-cell contacts. Products of PI 3-kinase activity also accumulate dynamically at contacts, but are not essential for either initiation or development of cell-cell adhesion. These results define a role for Rac1 in regulating the rates of initiation and strengthening of cell-cell adhesion.
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Rac was found at the membrane in control mice.
“Rac was found at the membrane in control mice, consistent with its function in cell-cell contact formation (Ehrlich et al, 2002).”
From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Ehrlich et al, 2002
The passage describing Figure 2A reports RacGFP accumulating along newly contacting membranes, supporting membrane localization during cell-cell contact formation. The Experimental Procedures describe cultured MDCK cells, not control mice; the source therefore does not support the claim's population or condition. (LLM, conf=0.88)
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References 49 · Cited by 358
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- Authors
- Ehrlich, J. S., Hansen, M. D. H., & Nelson, W. J.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Nelson, W.James
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 3
- Issue
- 2
- Pages
- 259-270
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC3369831
- OpenAlex
- W2009671568
- Cited by
- 358
- References
- 49
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 8 · 2023: 9 · 2022: 5 · 2021: 10 · 2020: 13 · 2019: 9 · 2018: 13 · 2017: 7 · 2016: 12 · 2015: 10 · 2014: 18 · 2013: 22 · 2012: 15
- FWCI
- 8.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 4003 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (GM35527)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- Rac1, lamellipodia, cell-cell adhesion, cadherins, epithelial cells, Rho GTPases, PI3-kinase, plasma membrane localization, MDCK cells, spatiotemporal control
- MeSH terms
- Phosphoinositide-3 Kinase Inhibitors, Actins, Animals, Biological Assay, Cell Adhesion, Cell Communication, Cell Compartmentation, Cell Membrane, Cell Movement, Enzyme Inhibitors, Epithelial Cells, Humans, Indicators and Reagents, Luminescent Proteins, Mutation, Pseudopodia, Time Factors, Microscopy, Video, Phosphatidylinositol 3-Kinases, rac1 GTP-Binding Protein, Green Fluorescent Proteins
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