Two Distinct Integrin-Mediated Mechanisms Contribute to Apical Lumen Formation in Epithelial Cells
Open accessAbstract
BACKGROUND: Formation of apical compartments underlies the morphogenesis of most epithelial organs during development. The extracellular matrix (ECM), particularly the basement membrane (BM), plays an important role in orienting the apico-basal polarity and thereby the positioning of apical lumens. Integrins have been recognized as essential mediators of matrix-derived polarity signals. The importance of β1-integrins in epithelial polarization is well established but the significance of the accompanying α-subunits have not been analyzed in detail. PRINCIPAL FINDINGS: Here we demonstrate that two distinct integrin-dependent pathways regulate formation of apical lumens to ensure robust apical membrane biogenesis under different microenvironmental conditions; 1) α2β1- and α6β4-integrins were required to establish a basal cue that depends on Rac1-activity and guides apico-basal cell polarization. 2) α3β1-integrins were implicated in positioning of mitotic spindles in cysts, a process that is essential for Cdc42-driven epithelial hollowing. SIGNIFICANCE: Identification of the separate processes driven by particular integrin receptors clarifies the functional hierarchies between the different integrins co-expressed in epithelial cells and provides valuable insight into the complexity of cell-ECM interactions thereby guiding future studies addressing the molecular basis of epithelial morphogenesis during development and disease.
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β4 integrin expressed by intestinal organoids is distributed only at the basal surface, while β1 integrin is required for proper apical-basal polarization.
“β4 integrin expressed by intestinal organoids is distributed only at the basal surface94, while β1 integrin is required for proper apical-basal polarization95–97.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [96]
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Towards organoid culture without Matrigel
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- Authors
- Myllymäki, S. M., Teräväinen, T. P., & Manninen, A.
- Affiliations
- University of Oulu (FI)
- Corresponding author
- Manninen, Aki
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-05-06
- Volume
- 6
- Issue
- 5
- Pages
- e19453
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3089628
- OpenAlex
- W2013419034
- Cited by
- 64
- References
- 53
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 8 · 2021: 1 · 2020: 3 · 2019: 6 · 2018: 6 · 2017: 6 · 2016: 3 · 2015: 6 · 2014: 3 · 2013: 4 · 2012: 5
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- 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 › Developmental Biology and Gene Regulation
- Keywords
- integrins, epithelial morphogenesis, apical-basal polarity, basement membrane, extracellular matrix, alpha2beta1 integrin, alpha6beta4 integrin, alpha3beta1 integrin, Rac1, Cdc42, mitotic spindle positioning, cell-matrix interactions, epithelial cysts
- MeSH terms
- Animals, Cell Adhesion, Cell Line, Dogs, Epithelial Cells, Fluorescent Antibody Technique, Microscopy, Fluorescence, Immunoblotting, Cell Polarity, Microscopy, Confocal, RNA, Small Interfering, Integrin alpha2beta1, Integrin alpha6beta4, Integrin alpha3beta1
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