The role of the cell adhesion molecule uvomorulin in the formation and maintenance of the epithelial junctional complex.
Open accessAbstract
The role of the epithelial adhesion molecule uvomorulin in the formation of the epithelial junctional complex in the Madin-Darby canine kidney (MDCK) cell line was investigated. Experiments were carried out to determine whether specific inhibition of uvomorulin function would interfere selectively with the formation, stability, or function of the apical zonula adherens (ZA) and zonula occludens (ZO), or whether it would interfere with all forms of intercellular contact including the desmosomes. The effects of blocking antibodies and Fab fragments to uvomorulin on the formation of the junctional complex was examined with a Ca2+ switch assay for de novo junction assembly. The formation of the ZO, the ZA, and the desmosomes was assayed by fluorescence staining with an antibody to the tight junction-specific protein ZO-1, with rhodamine-phalloidin for ZA-associated actin filaments, and with an anti-desmoplakin antibody, respectively. Under different conditions and times of antibody treatment the extent of inhibition of the formation of each of the junctional elements was very similar. The ability of the cells to eventually overcome the inhibitory effect of the antibodies and form junctions correlated with the reappearance of uvomorulin at the regions of cell-cell contact. Therefore uvomorulin seems to mediate an early adhesion event between epithelial cells that is a prerequisite for the assembly of all elements of the junctional complex. In contrast, the transepithelial electrical resistance of confluent, well-established monolayers of MDCK cells grown on filters was not greatly affected by treatment with the various antibodies or Fab fragments. A small transient decrease in resistance observed with the polyclonal alpha-uvomorulin IgG may be due to a more subtle modulation of the junctional complex.
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E-cadherin is a key determinant of junctional polarity in both simple and stratified epithelia.
“For example, E-cadherin is a key determinant of junctional polarity in both simple and stratified epithelia9, 34”
From E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning (2017) · cites this paper as [34]
The paper identifies uvomorulin as E-cadherin and reports that blocking it inhibits assembly of the junctional complex in MDCK epithelial cell monolayers (opening summary, p. 1575; Results, p. 1578). This supports a role in forming junctions, but the paper does not establish that E-cadherin determines junctional polarity in both simple and stratified epithelia; its experiments concern MDCK monolayers. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn vitro studies have shown that E-cadherin is necessary for adherens junction formation and its adhesive activity is crucial for assembly of desmosomes, gap junctions and tight junctions.
“In vitro studies have shown that E-cadherin is not only necessary for adherens junction formation but its adhesive activity is also crucial for the assembly of other junctional complexes such as desmosomes, gap junctions and tight junctions (Gumbiner et al, 1988;Musil et al, 1990;Watabe et al, 1994).”
From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Gumbiner et al, 1988
The paper identifies uvomorulin as E-cadherin, and its discussion concludes that formation of adherens junctions, desmosomes, and tight junctions similarly depends on uvomorulin function. It does not address gap-junction assembly, so that part of the claim is unsupported by this source. The supplied passages do not give a page number for the discussion. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn vitro studies using mostly simple epithelial cells have indicated that E-cadherin-mediated adhesion is a necessary prerequisite for the formation of other cell junctions, such as desmosomes, gap junctions and tight junctions.
“In vitro studies using mostly simple epithelial cells have indicated that E-cadherin-mediated adhesion is a necessary prerequisite for the formation of other cell junctions, such as desmosomes, gap junctions and tight junctions (Gumbiner et al, 1988;Musil et al, 1990;Watabe et al, 1994).”
From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Gumbiner et al, 1988
The Abstract (p. 1575) reports that blocking uvomorulin, also identified as E-cadherin, similarly inhibited formation of desmosomes and tight junctions in cultured MDCK epithelial cells. It does not report testing gap junction formation, so that part of the citing sentence is not supported by this paper. (LLM, conf=0.88)
Experimental — accuracy not yet measured
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- Authors
- Gumbiner, B., Stevenson, B., & Grimaldi, A.
- Affiliations
- University of California, San Francisco (US)
- ORCID
- Gumbiner, B
- Venue
- The Journal of cell biology
- Publisher
- Rockefeller University Press
- Published
- 1988-10-01
- Volume
- 107
- Issue
- 4
- Pages
- 1575-1587
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2115263
- OpenAlex
- W2114942120
- Cited by
- 799
- References
- 0
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 13 · 2020: 11 · 2019: 11 · 2018: 14 · 2017: 12 · 2016: 10 · 2015: 15 · 2014: 22 · 2013: 12 · 2012: 32
- FWCI
- 9.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2s07rr005355-30)
- National Institute of General Medical Sciences (GM37432)
- National Center for Research Resources (S07 RR-05355)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- uvomorulin, epithelial adhesion molecules, adherens junctions, zonula occludens, tight junctions, desmosomes, cell adhesion, MDCK cells, blocking antibodies, Fab fragment, transepithelial electrical resistance, ZO-1, desmoplakin, F-actin
- MeSH terms
- Animals, Calcium, Cell Adhesion, Cell Line, Desmosomes, Dogs, Epithelial Cells, Fluorescent Antibody Technique, Immunoglobulin Fab Fragments, Immunologic Techniques, Intercellular Junctions, Membrane Glycoproteins, Molecular Weight, Cadherins
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