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Gene Review

Cdh1  -  cadherin 1

Mus musculus

Synonyms: AA960649, ARC-1, Cadherin-1, E-cad, E-cadherin, ...
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Disease relevance of Cdh1

  • Intracellular domain of desmoglein 3 (pemphigus vulgaris antigen) confers adhesive function on the extracellular domain of E-cadherin without binding catenins [1].
  • We constructed recombinant adenoviruses (Ad) containing truncated mutants of E-cadherin, desmocollin 3a, and desmoglein 3 lacking a large part of their extracellular domains (EcaddeltaEC, Dsc3adeltaEC, Dsg3deltaEC), using the Cre-loxP Ad system to circumvent the problem of the toxicity of the mutants to virus-producing cells [2].
  • (3) In addition to its high expression in surface ectoderm-derived tissues, E-cadherin mRNA was also detected in some of the retinal ganglion neurons at postnatal day 14 (P14) [3].
  • The next challenge is to define which secreted agents implicated in hair growth control modulate these follicular cadherin expression patterns, and to define how these basic parameters of HF topobiology are altered during common hair growth disorders [4].
  • Epithelial-mesenchymal transitions are also determinants of the progression of carcinomas, occurring concomitantly with the cellular acquisition of migratory properties following downregulation of expression of the adhesion protein E-cadherin [5].

Psychiatry related information on Cdh1


High impact information on Cdh1

  • p38 and a p38-interacting protein are critical for downregulation of E-cadherin during mouse gastrulation [7].
  • A stronger allele (p38IP(RRK)) exhibits gastrulation defects in which mesoderm migration is defective due to deficiency in E-cadherin protein downregulation in the primitive streak [7].
  • Moreover, both p38 and p38IP are required for E-cadherin downregulation during gastrulation [7].
  • Direct analysis in polarized cells shows that mobilities of E-cadherin, beta-catenin, and alpha-catenin are similar, regardless of the dynamic state of actin assembly, whereas actin and several actin binding proteins have higher mobilities [8].
  • Spatial and functional organization of cells in tissues is determined by cell-cell adhesion, thought to be initiated through trans-interactions between extracellular domains of the cadherin family of adhesion proteins, and strengthened by linkage to the actin cytoskeleton [8].

Chemical compound and disease context of Cdh1


Biological context of Cdh1

  • Finally, we show that Emi1-dependent effects on meiosis I require the presence of Cdh1 [14].
  • These observations reveal an intrinsic late-G1-phase checkpoint, after transition across the growth factor-dependent G1 restriction point, that links increased steady-state levels of endogenous ROS and cell cycle progression through continued activity of APC in association with Cdh1 [15].
  • The E-cadherin cell adhesion molecule is associated with cytoplasmic polypeptides, and this association is essential for its cell-binding function [16].
  • Vascular endothelial cadherin, VE-cadherin, mediates adhesion between endothelial cells and may affect vascular morphogenesis via intracellular signaling, but the nature of these signals remains unknown [17].
  • BACKGROUND & AIMS: Inactivation of the adenomatous polyposis coli (APC) gene is observed at early stages of intestinal tumor formation, whereas loss of E-cadherin is usually associated with tumor progression [18].

Anatomical context of Cdh1

  • We have isolated a novel actin filament-binding protein, named afadin, localized at cadherin-based cell-cell adherens junctions (AJs) in various tissues and cell lines [19].
  • In this study, we identified a novel class of cadherin, termed P-cadherin, using a visceral endoderm cell line PSA5-E [20].
  • We show here that the full IC domain of PVA as well as an IC subdomain containing only 40 amino acids of the PVA intracellular anchor (IA) region confer adhesive function on the E-cadherin EC domain without catenin-like associations with cytoplasmic molecules or fractionation with the cell cytoskeleton [1].
  • Although beta-catenin interacts tightly with E-cadherin, it does not seem to be associated with either desmoglein I or with isolated desmosomes [21].
  • To test this hypothesis we studied aggregation of mouse fibroblast L cell clones that expressed chimeric cDNAs encoding the EC domain of E-cadherin with various IC domains [1].

Associations of Cdh1 with chemical compounds


Physical interactions of Cdh1


Enzymatic interactions of Cdh1


Co-localisations of Cdh1


Regulatory relationships of Cdh1

  • CONCLUSIONS: Introduction of the E-cadherin mutation in Apc1638N animals enhances Apc-driven tumor initiation without clearly affecting tumor progression [18].
  • Ultimately, cadherin-6 is down-regulated whereas E-cadherin expression remains in most, if not all, of the tubular epithelium [34].
  • A fragment of N-cadherin lacking its extracellular region serves as a dominant negative mutant (DN) and inhibits cell-cell adhesion activity of E-cadherin, but its mode of action remains to be elucidated [35].
  • Moreover, overexpression of nectin enhanced the E-cadherin-based cell-cell adhesion activity [35].
  • Ksp- and LI-cadherin are structurally homologous proteins coexpressed with E-cadherin in renal and intestinal epithelia, respectively [36].

Other interactions of Cdh1


Analytical, diagnostic and therapeutic context of Cdh1


  1. Intracellular domain of desmoglein 3 (pemphigus vulgaris antigen) confers adhesive function on the extracellular domain of E-cadherin without binding catenins. Roh, J.Y., Stanley, J.R. J. Cell Biol. (1995) [Pubmed]
  2. Different effects of dominant negative mutants of desmocollin and desmoglein on the cell-cell adhesion of keratinocytes. Hanakawa, Y., Amagai, M., Shirakata, Y., Sayama, K., Hashimoto, K. J. Cell. Sci. (2000) [Pubmed]
  3. Systematic analysis of E-, N- and P-cadherin expression in mouse eye development. Xu, L., Overbeek, P.A., Reneker, L.W. Exp. Eye Res. (2002) [Pubmed]
  4. E- and P-cadherin expression during murine hair follicle morphogenesis and cycling. Müller-Röver, S., Tokura, Y., Welker, P., Furukawa, F., Wakita, H., Takigawa, M., Paus, R. Exp. Dermatol. (1999) [Pubmed]
  5. The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Cano, A., Pérez-Moreno, M.A., Rodrigo, I., Locascio, A., Blanco, M.J., del Barrio, M.G., Portillo, F., Nieto, M.A. Nat. Cell Biol. (2000) [Pubmed]
  6. Expression of dominant negative cadherin in the adult mouse brain modifies rearing behavior. Edsbagge, J., Zhu, S., Xiao, M.Y., Wigström, H., Mohammed, A.H., Semb, H. Mol. Cell. Neurosci. (2004) [Pubmed]
  7. p38 and a p38-interacting protein are critical for downregulation of E-cadherin during mouse gastrulation. Zohn, I.E., Li, Y., Skolnik, E.Y., Anderson, K.V., Han, J., Niswander, L. Cell (2006) [Pubmed]
  8. Deconstructing the cadherin-catenin-actin complex. Yamada, S., Pokutta, S., Drees, F., Weis, W.I., Nelson, W.J. Cell (2005) [Pubmed]
  9. Mechanism of activation of the ret proto-oncogene by multiple endocrine neoplasia 2A mutations. Asai, N., Iwashita, T., Matsuyama, M., Takahashi, M. Mol. Cell. Biol. (1995) [Pubmed]
  10. The plant lectin wheat germ agglutinin inhibits the binding of pemphigus foliaceus autoantibodies to desmoglein 1 in a majority of patients and prevents pathomechanisms of pemphigus foliaceus in vitro and in vivo. Ortiz-Urda, S., Elbe-Bürger, A., Smolle, J., Marquart, Y., Chudnovsky, Y., Ridky, T.W., Bernstein, P., Wolff, K., Rappersberger, K. J. Immunol. (2003) [Pubmed]
  11. The addition of bisecting N-acetylglucosamine residues to E-cadherin down-regulates the tyrosine phosphorylation of beta-catenin. Kitada, T., Miyoshi, E., Noda, K., Higashiyama, S., Ihara, H., Matsuura, N., Hayashi, N., Kawata, S., Matsuzawa, Y., Taniguchi, N. J. Biol. Chem. (2001) [Pubmed]
  12. E-cadherin is a ligand for integrin alpha2beta1. Whittard, J.D., Craig, S.E., Mould, A.P., Koch, A., Pertz, O., Engel, J., Humphries, M.J. Matrix Biol. (2002) [Pubmed]
  13. Effects of cadmium on E-cadherin and VE-cadherin in mouse lung. Pearson, C.A., Lamar, P.C., Prozialeck, W.C. Life Sci. (2003) [Pubmed]
  14. Prophase I arrest and progression to metaphase I in mouse oocytes are controlled by Emi1-dependent regulation of APCCdh1. Marangos, P., Verschuren, E.W., Chen, R., Jackson, P.K., Carroll, J. J. Cell Biol. (2007) [Pubmed]
  15. Regulation of late G1/S phase transition and APC Cdh1 by reactive oxygen species. Havens, C.G., Ho, A., Yoshioka, N., Dowdy, S.F. Mol. Cell. Biol. (2006) [Pubmed]
  16. The 102 kd cadherin-associated protein: similarity to vinculin and posttranscriptional regulation of expression. Nagafuchi, A., Takeichi, M., Tsukita, S. Cell (1991) [Pubmed]
  17. Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Carmeliet, P., Lampugnani, M.G., Moons, L., Breviario, F., Compernolle, V., Bono, F., Balconi, G., Spagnuolo, R., Oostuyse, B., Dewerchin, M., Zanetti, A., Angellilo, A., Mattot, V., Nuyens, D., Lutgens, E., Clotman, F., de Ruiter, M.C., Gittenberger-de Groot, A., Poelmann, R., Lupu, F., Herbert, J.M., Collen, D., Dejana, E. Cell (1999) [Pubmed]
  18. E-cadherin and adenomatous polyposis coli mutations are synergistic in intestinal tumor initiation in mice. Smits, R., Ruiz, P., Diaz-Cano, S., Luz, A., Jagmohan-Changur, S., Breukel, C., Birchmeier, C., Birchmeier, W., Fodde, R. Gastroenterology (2000) [Pubmed]
  19. Nectin/PRR: an immunoglobulin-like cell adhesion molecule recruited to cadherin-based adherens junctions through interaction with Afadin, a PDZ domain-containing protein. Takahashi, K., Nakanishi, H., Miyahara, M., Mandai, K., Satoh, K., Satoh, A., Nishioka, H., Aoki, J., Nomoto, A., Mizoguchi, A., Takai, Y. J. Cell Biol. (1999) [Pubmed]
  20. A novel cadherin cell adhesion molecule: its expression patterns associated with implantation and organogenesis of mouse embryos. Nose, A., Takeichi, M. J. Cell Biol. (1986) [Pubmed]
  21. The vertebrate adhesive junction proteins beta-catenin and plakoglobin and the Drosophila segment polarity gene armadillo form a multigene family with similar properties. Peifer, M., McCrea, P.D., Green, K.J., Wieschaus, E., Gumbiner, B.M. J. Cell Biol. (1992) [Pubmed]
  22. Expression and role of E- and P-cadherin adhesion molecules in embryonic histogenesis. I. Lung epithelial morphogenesis. Hirai, Y., Nose, A., Kobayashi, S., Takeichi, M. Development (1989) [Pubmed]
  23. Regulation of complexed and free catenin pools by distinct mechanisms. Differential effects of Wnt-1 and v-Src. Papkoff, J. J. Biol. Chem. (1997) [Pubmed]
  24. Thermodynamics of beta-catenin-ligand interactions: the roles of the N- and C-terminal tails in modulating binding affinity. Choi, H.J., Huber, A.H., Weis, W.I. J. Biol. Chem. (2006) [Pubmed]
  25. Alteration of E-cadherin and alpha N-catenin immunoreactivity in the mouse spinal cord following peripheral axotomy. Seto, A., Hasegawa, M., Uchiyama, N., Yamashima, T., Yamashita, J. J. Neuropathol. Exp. Neurol. (1997) [Pubmed]
  26. Continuous association of cadherin with beta-catenin requires the non-receptor tyrosine-kinase Fer. Xu, G., Craig, A.W., Greer, P., Miller, M., Anastasiadis, P.Z., Lilien, J., Balsamo, J. J. Cell. Sci. (2004) [Pubmed]
  27. Cadherin/catenin complexes in murine epidermal keratinocytes: E-cadherin complexes containing either beta-catenin or plakoglobin contribute to stable cell-cell contacts. Lozano, E., Cano, A. Cell Adhes. Commun. (1998) [Pubmed]
  28. Mouse ribonucleotide reductase R2 protein: a new target for anaphase-promoting complex-Cdh1-mediated proteolysis. Chabes, A.L., Pfleger, C.M., Kirschner, M.W., Thelander, L. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  29. Ectodomain shedding of nectin-1alpha by SF/HGF and TPA in MDCK cells. Tanaka, Y., Irie, K., Hirota, T., Sakisaka, T., Nakanishi, H., Takai, Y. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  30. Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways. Gavard, J., Lambert, M., Grosheva, I., Marthiens, V., Irinopoulou, T., Riou, J.F., Bershadsky, A., Mège, R.M. J. Cell. Sci. (2004) [Pubmed]
  31. Identification of cadherin tyrosine residues that are phosphorylated and mediate Shc association. Xu, Y., Carpenter, G. J. Cell. Biochem. (1999) [Pubmed]
  32. Tyrosine phosphorylation and src family kinases control keratinocyte cell-cell adhesion. Calautti, E., Cabodi, S., Stein, P.L., Hatzfeld, M., Kedersha, N., Paolo Dotto, G. J. Cell Biol. (1998) [Pubmed]
  33. BDNF/NT4-5 receptor TrkB and cadherin participate in cell-cell adhesion. Zhou, H., Welcher, A.A., Shooter, E.M. J. Neurosci. Res. (1997) [Pubmed]
  34. Differential expression and function of cadherin-6 during renal epithelium development. Cho, E.A., Patterson, L.T., Brookhiser, W.T., Mah, S., Kintner, C., Dressler, G.R. Development (1998) [Pubmed]
  35. Role of nectin in formation of E-cadherin-based adherens junctions in keratinocytes: analysis with the N-cadherin dominant negative mutant. Tanaka, Y., Nakanishi, H., Kakunaga, S., Okabe, N., Kawakatsu, T., Shimizu, K., Takai, Y. Mol. Biol. Cell (2003) [Pubmed]
  36. Ksp-cadherin is a functional cell-cell adhesion molecule related to LI-cadherin. Wendeler, M.W., Praus, M., Jung, R., Hecking, M., Metzig, C., Gessner, R. Exp. Cell Res. (2004) [Pubmed]
  37. Requirement for beta-catenin in anterior-posterior axis formation in mice. Huelsken, J., Vogel, R., Brinkmann, V., Erdmann, B., Birchmeier, C., Birchmeier, W. J. Cell Biol. (2000) [Pubmed]
  38. Cadherins regulate aggregation of pancreatic beta-cells in vivo. Dahl, U., Sjødin, A., Semb, H. Development (1996) [Pubmed]
  39. Wnt-1-dependent regulation of local E-cadherin and alpha N-catenin expression in the embryonic mouse brain. Shimamura, K., Hirano, S., McMahon, A.P., Takeichi, M. Development (1994) [Pubmed]
  40. Chromosomal mapping of the structural gene coding for the mouse cell adhesion molecule uvomorulin. Eistetter, H.R., Adolph, S., Ringwald, M., Simon-Chazottes, D., Schuh, R., Guénet, J.L., Kemler, R. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  41. Molecular cloning and expression of murine vascular endothelial-cadherin in early stage development of cardiovascular system. Breier, G., Breviario, F., Caveda, L., Berthier, R., Schnürch, H., Gotsch, U., Vestweber, D., Risau, W., Dejana, E. Blood (1996) [Pubmed]
  42. Genetic dissection of cadherin function during nephrogenesis. Dahl, U., Sjödin, A., Larue, L., Radice, G.L., Cajander, S., Takeichi, M., Kemler, R., Semb, H. Mol. Cell. Biol. (2002) [Pubmed]
  43. Defects in cell adhesion and the visceral endoderm following ablation of nonmuscle myosin heavy chain II-A in mice. Conti, M.A., Even-Ram, S., Liu, C., Yamada, K.M., Adelstein, R.S. J. Biol. Chem. (2004) [Pubmed]
  44. Involvement of R-cadherin in the early stage of glomerulogenesis. Goto, S., Yaoita, E., Matsunami, H., Kondo, D., Yamamoto, T., Kawasaki, K., Arakawa, M., Kihara, I. J. Am. Soc. Nephrol. (1998) [Pubmed]
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