Development, Vol 102, Issue 4 639-655, Copyright © 1988 by Company of Biologists

JOURNAL ARTICLES

The cadherins: cell-cell adhesion molecules controlling animal morphogenesis

M Takeichi
Department of Biophysics, Faculty of Science, Kyoto University, Japan.

Cadherins are a family of glycoproteins involved in the Ca2+-dependent cell-cell adhesion mechanism which is detected in most kinds of tissues. Inhibition of the cadherin activity with antibodies induces dissociation of cell layers, indicating a fundamental importance of these molecules in maintaining the multicellular structure. Cadherins are divided into subclasses, including E-, N- and P-cadherins. While all subclasses are similar in molecular weight, Ca2+- and protease-sensitivity, each subclass is characterized by a unique tissue distribution pattern and immunological specificity. Analysis of amino acid sequences deduced from cDNA encoding these molecules showed that they are integral membrane proteins of 723-748 amino acids long and share common sequences; similarity in the sequences between subclasses is in a range of 50-60% when compared within a single animal species. L cells, with very little endogenous cadherin activity, transfected with the cadherin cDNA acquired high cadherin-mediated aggregating activity. Their colony morphology was altered by the ectopic expression of cadherins from the dispersed type to the compact type, providing direct evidence for a key role of cadherins in cell-cell adhesion. It has been suggested that cadherins bind cells by their homophilic interactions at the extracellular domain and are associated with actin bundles at the cytoplasmic domain. It appears that each cadherin subclass has binding specificity and this molecular family is involved in selective cell-cell adhesion. In development, the expression of each cadherin subclass is spatiotemporally regulated and associated with a variety of morphogenetic events; e.g. the termination or initiation of expression of a cadherin subclass in a given cell collective is correlated with its segregation from or connection with other cell collectives. Antibodies to cadherins were shown to perturb the morphogenesis of some embryonic organs in vitro. These observations suggest that cadherins play a crucial role in construction of tissues and the whole animal body.
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				Y. Shimoyama, H. Takeda, S. Yoshihara, M. Kitajima, and S. Hirohashi Biochemical Characterization and Functional Analysis of Two Type II Classic Cadherins, Cadherin-6 and -14, and Comparison with E-cadherin J. Biol. Chem., April 23, 1999; 274(17): 11987 - 11994. [Abstract] [Full Text] [PDF]

				K. Mandai, H. Nakanishi, A. Satoh, K. Takahashi, K. Satoh, H. Nishioka, A. Mizoguchi, and Y. Takai Ponsin/SH3P12: An l-Afadin- and Vinculin-binding Protein Localized at Cell-Cell and Cell-Matrix Adherens Junctions J. Cell Biol., March 8, 1999; 144(5): 1001 - 1018. [Abstract] [Full Text] [PDF]

				J. A. Efstathiou, D. Liu, J. M. D. Wheeler, H. C. Kim, N. E. Beck, M. Ilyas, A. J. Karayiannakis, N. J. McC. Mortensen, W. Kmiot, R. J. Playford, et al. Mutated epithelial cadherin is associated with increased tumorigenicity and loss of adhesion and of responsiveness to the motogenic trefoil factor 2 in colon carcinoma cells PNAS, March 2, 1999; 96(5): 2316 - 2321. [Abstract] [Full Text] [PDF]

				M. J. Pishvaian, C. M. Feltes, P. Thompson, M. J. Bussemakers, J. A. Schalken, and S. W. Byers Cadherin-11 Is Expressed in Invasive Breast Cancer Cell Lines Cancer Res., February 1, 1999; 59(4): 947 - 952. [Abstract] [Full Text] [PDF]

				S. Hirano, Q. Yan, and S. T. Suzuki Expression of a Novel Protocadherin, OL-Protocadherin, in a Subset of Functional Systems of the Developing Mouse Brain J. Neurosci., February 1, 1999; 19(3): 995 - 1005. [Abstract] [Full Text] [PDF]

				D Sela-Donenfeld and C Kalcheim Regulation of the onset of neural crest migration by coordinated activity of BMP4 and Noggin in the dorsal neural tube Development, January 11, 1999; 126(21): 4749 - 4762. [Abstract] [PDF]

				H. Kuniyasu, L. M. Ellis, D. B. Evans, J. L. Abbruzzese, C. J. Fenoglio, C. D. Bucana, K. R. Cleary, E. Tahara, and I. J. Fidler Relative Expression of E-Cadherin and Type IV Collagenase Genes Predicts Disease Outcome in Patients with Resectable Pancreatic Carcinoma Clin. Cancer Res., January 1, 1999; 5(1): 25 - 33. [Abstract] [Full Text] [PDF]

				T. Ohtsuka, H. Nakanishi, W. Ikeda, A. Satoh, Y. Momose, H. Nishioka, and Y. Takai Nexilin: A Novel Actin Filament-binding Protein Localized at Cell-Matrix Adherens Junction J. Cell Biol., November 30, 1998; 143(5): 1227 - 1238. [Abstract] [Full Text] [PDF]

				R. Pey, C. Vial, G. Schatten, and M. Hafner Increase of intracellular Ca2+ and relocation of E-cadherin during experimental decompaction of mouse embryos PNAS, October 27, 1998; 95(22): 12977 - 12982. [Abstract] [Full Text] [PDF]

				Y. V. Bobryshev, R. S.A. Lord, T. Watanabe, and T. Ikezawa The cell adhesion molecule E-cadherin is widely expressed in human atherosclerotic lesions Cardiovasc Res, October 1, 1998; 40(1): 191 - 205. [Abstract] [Full Text] [PDF]

				J. Grima, C. C. S. Wong, L.-j. Zhu, S.-d. Zong, and C. Y. Cheng Testin Secreted by Sertoli Cells Is Associated with the Cell Surface, and Its Expression Correlates with the Disruption of Sertoli-Germ Cell Junctions but Not the Inter-Sertoli Tight Junction J. Biol. Chem., August 14, 1998; 273(33): 21040 - 21053. [Abstract] [Full Text] [PDF]

				M. Watabe-Uchida, N. Uchida, Y. Imamura, A. Nagafuchi, K. Fujimoto, T. Uemura, S. Vermeulen, F. van Roy, E. D. Adamson, and M. Takeichi {alpha}-Catenin-Vinculin Interaction Functions to Organize the Apical Junctional Complex in Epithelial Cells J. Cell Biol., August 10, 1998; 142(3): 847 - 857. [Abstract] [Full Text] [PDF]

				S. Hirohashi Inactivation of the E-Cadherin-Mediated Cell Adhesion System in Human Cancers Am. J. Pathol., August 1, 1998; 153(2): 333 - 339. [Abstract] [Full Text] [PDF]

				E. Calautti, S. Cabodi, P. L. Stein, M. Hatzfeld, N. Kedersha, and G. Paolo Dotto Tyrosine Phosphorylation and Src Family Kinases Control Keratinocyte Cell-Cell Adhesion J. Cell Biol., June 15, 1998; 141(6): 1449 - 1465. [Abstract] [Full Text] [PDF]