Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1992 Apr 2;117(2):415–425. doi: 10.1083/jcb.117.2.415

Regulation of keratinocyte intercellular junction organization and epidermal morphogenesis by E-cadherin

PMCID: PMC2289421  PMID: 1373144

Abstract

Elevation of the calcium concentration in human keratinocyte culture rapidly induces the redistribution of E-cadherin, P-cadherin, vinculin, beta 1 integrin, and desmoplakin to the cell-cell borders. Antibody to E-cadherin that blocks its functional activity delays the redistribution of each marker by several hours. Furthermore, antibody to E-cadherin interferes with normal, calcium-induced stratification of keratinocytes. Although several uneven vertical layers of cells can be detected in the presence of anti-E-cadherin antibody, the superficial cells appear defective in their adhesion. They do not flatten upon the basal layer nor do they enlarge, as do the controls; but rather they remain in groups of small cells connected by a line of single cells or by very long processes. In spite of the deformed appearance of the superficial cells in the presence of anti-E-cadherin IgG, these cells express the differentiation marker filaggrin, do not express P- cadherin, and concentrate desmoplakin at their cell-cell borders, consistent with the pattern in normally stratified cultures and in epidermis. These studies suggest a central role for E-cadherin in the regulation of keratinocyte intercellular junction organization as well as in epidermal morphogenesis.

Full Text

The Full Text of this article is available as a PDF (2.1 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amagai M., Klaus-Kovtun V., Stanley J. R. Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion. Cell. 1991 Nov 29;67(5):869–877. doi: 10.1016/0092-8674(91)90360-b. [DOI] [PubMed] [Google Scholar]
  2. Banks-Schlegel S., Green H. Involucrin synthesis and tissue assembly by keratinocytes in natural and cultured human epithelia. J Cell Biol. 1981 Sep;90(3):732–737. doi: 10.1083/jcb.90.3.732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boyce S. T., Ham R. G. Calcium-regulated differentiation of normal human epidermal keratinocytes in chemically defined clonal culture and serum-free serial culture. J Invest Dermatol. 1983 Jul;81(1 Suppl):33s–40s. doi: 10.1111/1523-1747.ep12540422. [DOI] [PubMed] [Google Scholar]
  4. Carter W. G., Wayner E. A., Bouchard T. S., Kaur P. The role of integrins alpha 2 beta 1 and alpha 3 beta 1 in cell-cell and cell-substrate adhesion of human epidermal cells. J Cell Biol. 1990 Apr;110(4):1387–1404. doi: 10.1083/jcb.110.4.1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chen W. C., Obrink B. Cell-cell contacts mediated by E-cadherin (uvomorulin) restrict invasive behavior of L-cells. J Cell Biol. 1991 Jul;114(2):319–327. doi: 10.1083/jcb.114.2.319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fleckman P., Dale B. A., Holbrook K. A. Profilaggrin, a high-molecular-weight precursor of filaggrin in human epidermis and cultured keratinocytes. J Invest Dermatol. 1985 Dec;85(6):507–512. doi: 10.1111/1523-1747.ep12277306. [DOI] [PubMed] [Google Scholar]
  7. Frixen U. H., Behrens J., Sachs M., Eberle G., Voss B., Warda A., Löchner D., Birchmeier W. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 1991 Apr;113(1):173–185. doi: 10.1083/jcb.113.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Green H., Kehinde O., Thomas J. Growth of cultured human epidermal cells into multiple epithelia suitable for grafting. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5665–5668. doi: 10.1073/pnas.76.11.5665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gumbiner B., Stevenson B., Grimaldi A. The role of the cell adhesion molecule uvomorulin in the formation and maintenance of the epithelial junctional complex. J Cell Biol. 1988 Oct;107(4):1575–1587. doi: 10.1083/jcb.107.4.1575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hennings H., Holbrook K. A. Calcium regulation of cell-cell contact and differentiation of epidermal cells in culture. An ultrastructural study. Exp Cell Res. 1983 Jan;143(1):127–142. doi: 10.1016/0014-4827(83)90115-5. [DOI] [PubMed] [Google Scholar]
  11. Hennings H., Michael D., Cheng C., Steinert P., Holbrook K., Yuspa S. H. Calcium regulation of growth and differentiation of mouse epidermal cells in culture. Cell. 1980 Jan;19(1):245–254. doi: 10.1016/0092-8674(80)90406-7. [DOI] [PubMed] [Google Scholar]
  12. Hirai Y., Nose A., Kobayashi S., Takeichi M. Expression and role of E- and P-cadherin adhesion molecules in embryonic histogenesis. II. Skin morphogenesis. Development. 1989 Feb;105(2):271–277. doi: 10.1242/dev.105.2.271. [DOI] [PubMed] [Google Scholar]
  13. Jongen W. M., Fitzgerald D. J., Asamoto M., Piccoli C., Slaga T. J., Gros D., Takeichi M., Yamasaki H. Regulation of connexin 43-mediated gap junctional intercellular communication by Ca2+ in mouse epidermal cells is controlled by E-cadherin. J Cell Biol. 1991 Aug;114(3):545–555. doi: 10.1083/jcb.114.3.545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  15. Larjava H., Peltonen J., Akiyama S. K., Yamada S. S., Gralnick H. R., Uitto J., Yamada K. M. Novel function for beta 1 integrins in keratinocyte cell-cell interactions. J Cell Biol. 1990 Mar;110(3):803–815. doi: 10.1083/jcb.110.3.803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Marchisio P. C., Bondanza S., Cremona O., Cancedda R., De Luca M. Polarized expression of integrin receptors (alpha 6 beta 4, alpha 2 beta 1, alpha 3 beta 1, and alpha v beta 5) and their relationship with the cytoskeleton and basement membrane matrix in cultured human keratinocytes. J Cell Biol. 1991 Feb;112(4):761–773. doi: 10.1083/jcb.112.4.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McNeill H., Jensen P. J. A high-affinity receptor for urokinase plasminogen activator on human keratinocytes: characterization and potential modulation during migration. Cell Regul. 1990 Oct;1(11):843–852. doi: 10.1091/mbc.1.11.843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nicholson L. J., Pei X. F., Watt F. M. Expression of E-cadherin, P-cadherin and involucrin by normal and neoplastic keratinocytes in culture. Carcinogenesis. 1991 Jul;12(7):1345–1349. doi: 10.1093/carcin/12.7.1345. [DOI] [PubMed] [Google Scholar]
  19. O'Keefe E. J., Briggaman R. A., Herman B. Calcium-induced assembly of adherens junctions in keratinocytes. J Cell Biol. 1987 Aug;105(2):807–817. doi: 10.1083/jcb.105.2.807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pillai S., Bikle D. D., Hincenbergs M., Elias P. M. Biochemical and morphological characterization of growth and differentiation of normal human neonatal keratinocytes in a serum-free medium. J Cell Physiol. 1988 Feb;134(2):229–237. doi: 10.1002/jcp.1041340208. [DOI] [PubMed] [Google Scholar]
  21. Shimoyama Y., Hirohashi S., Hirano S., Noguchi M., Shimosato Y., Takeichi M., Abe O. Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas. Cancer Res. 1989 Apr 15;49(8):2128–2133. [PubMed] [Google Scholar]
  22. Shipley G. D., Pittelkow M. R. Control of growth and differentiation in vitro of human keratinocytes cultured in serum-free medium. Arch Dermatol. 1987 Nov;123(11):1541a–1544a. [PubMed] [Google Scholar]
  23. Takeichi M. The cadherins: cell-cell adhesion molecules controlling animal morphogenesis. Development. 1988 Apr;102(4):639–655. doi: 10.1242/dev.102.4.639. [DOI] [PubMed] [Google Scholar]
  24. Tsao M. C., Walthall B. J., Ham R. G. Clonal growth of normal human epidermal keratinocytes in a defined medium. J Cell Physiol. 1982 Feb;110(2):219–229. doi: 10.1002/jcp.1041100217. [DOI] [PubMed] [Google Scholar]
  25. Vleminckx K., Vakaet L., Jr, Mareel M., Fiers W., van Roy F. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell. 1991 Jul 12;66(1):107–119. doi: 10.1016/0092-8674(91)90143-m. [DOI] [PubMed] [Google Scholar]
  26. Watt F. M., Mattey D. L., Garrod D. R. Calcium-induced reorganization of desmosomal components in cultured human keratinocytes. J Cell Biol. 1984 Dec;99(6):2211–2215. doi: 10.1083/jcb.99.6.2211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wheelock M. J., Buck C. A., Bechtol K. B., Damsky C. H. Soluble 80-kd fragment of cell-CAM 120/80 disrupts cell-cell adhesion. J Cell Biochem. 1987 Jul;34(3):187–202. doi: 10.1002/jcb.240340305. [DOI] [PubMed] [Google Scholar]
  28. Wheelock M. J., Knudsen K. A. Cadherins and associated proteins. In Vivo. 1991 Sep-Oct;5(5):505–513. [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES