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Gene Review

Cdh2  -  cadherin 2

Mus musculus

Synonyms: CDHN, Cadherin-2, N-cadherin, Ncad, Neural cadherin
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Disease relevance of Cdh2

  • S1P-induced trafficking and activation of N-cadherin provides a novel mechanism for the stabilization of nascent blood vessels by mural cells and may be exploited to control angiogenesis and vascular diseases [1].
  • MATERIALS AND METHODS: It has been previously reported that N-cadherin-expressing E-cadherin-/- ES transfectants formed neuroepithelium and cartilage in teratomas [2].
  • In vivo analysis showed that N-cadherin- and cadherin-11-overexpressing cells exhibited a marked reduction in their ability to form pulmonary metastases, with significant decreases in lung weight and the number and weight of metastatic lesions, as well as the size and weight of primary lesions at the s.c.-inoculated site [3].
  • These observations demonstrate that disruption of N-cadherin- and cadherin-11-mediated cell-cell adhesion is critical in the pulmonary metastasis of osteosarcoma [3].
  • The N-cadherin-positive carcinoma cell line, PC-3N, displayed aggressive invasion into the surface of the diaphragm muscle after intraperitoneal injection of SCID mice [4].

Psychiatry related information on Cdh2

  • Presenilin1 (PS1), a protein implicated in Alzheimer's disease (AD), forms complexes with N-cadherin, a transmembrane protein with important neuronal and synaptic functions [5].

High impact information on Cdh2


Biological context of Cdh2

  • CONCLUSIONS: Cdh2 is involved in the homeostatic bone formation response to ovariectomy, presumably by regulating osteoprogenitors number and differentiation through stabilization of cell-cell adhesion and/or signaling modulation [9].
  • Although development of calcified nodules was faster in calvaria cells isolated from Cdh2+/- mice relative to Cdh2+/+ cells, bone marrow osteogenic precursors were lower in the former than in the latter genotypes [9].
  • In this study, we determined the structure of the mouse N-cadherin gene by analyzing overlapping genomic clones obtained from a mouse genomic library [10].
  • This large size of the N-cadherin gene, compared with its cDNA (4.3 kilobases), is ascribed to the fact that the first and second introns are 34.2 kilobases and greater than 100 kilobases long, respectively [10].
  • We also determined the chromosomal localization of the N-cadherin gene by interspecific backcross analysis and found that this gene is localized in the proximal region of mouse chromosome 18 [10].

Anatomical context of Cdh2

  • Cdh2 expression was downregulated with differentiation in wildtype calvaria cells, whereas cadherin-11 abundance remained unchanged [9].
  • Ovariectomy-induced bone loss is accentuated in mice with germline Cdh2 haploinsufficiency, the result of a decreased osteoblastogenesis in the face of normal osteoclast number [9].
  • The net result of endothelial cell S1P1 receptor activation is the proper trafficking and strengthening of N-cadherin-dependent cell-cell adhesion with mural cells [1].
  • Expression of the truncated E-cadherin receptor displaced both E- and N-cadherin from pancreatic beta-cells [11].
  • Mouse primary myoblast cultures exhibited similar responses to N-cadherin as C2 cells [12].

Associations of Cdh2 with chemical compounds

  • In addition, p120(ctn) connected with N-cadherin was phosphorylated at tyrosine residues, whereas the isoform linked to E-cadherin was not phosphorylated [13].
  • In contrast, with NMDA application, N-cadherin does not disperse but does acquire enhanced protease resistance and dimerizes [14].
  • The same peptide has no effect on integrin dependent neurite outgrowth or neurite outgrowth stimulated by N-cadherin or L1 [15].
  • In extracts of eggs and midblastula stage embryos the antipeptide antibody recognized specifically a 120-kD glycoprotein that migrated faster on SDS gels than the 140-kD E- and N-cadherin polypeptides [16].
  • GC migration mediated by L1 and Ncad but not by beta1 integrin is inhibited after DRM disruption by micro-scale chromophore-assisted laser inactivation (micro-CALI) of GM1 gangliosides or by pharmacological treatments that deplete cellular cholesterol or sphingolipids, essential components for DRMs [17].

Physical interactions of Cdh2


Regulatory relationships of Cdh2

  • 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 [21].
  • These results suggest that cadherin-11 directly regulates the differentiation of mesenchymal cells into the cells of the osteo-lineage and the chondro-lineage in a different manner from N-cadherin [2].
  • N-cadherin is expressed in the inner layer and P-cadherin in the outer layer of the ciliary epithelium [22].
  • RESULTS: We show here that the levels of N-cadherin are downregulated in calreticulin-deficient mouse embryonic hearts, which may lead to the disarray and wavy appearance of myofibrils in these mice, which we detected at all investigated stages of cardiac development [23].
  • RhoA/ROCK and Cdc42 regulate cell-cell contact and N-cadherin protein level during neurodetermination of P19 embryonal stem cells [24].

Other interactions of Cdh2


Analytical, diagnostic and therapeutic context of Cdh2


  1. Sphingosine 1-phosphate receptor regulation of N-cadherin mediates vascular stabilization. Paik, J.H., Skoura, A., Chae, S.S., Cowan, A.E., Han, D.K., Proia, R.L., Hla, T. Genes Dev. (2004) [Pubmed]
  2. Cell-cell interaction mediated by cadherin-11 directly regulates the differentiation of mesenchymal cells into the cells of the osteo-lineage and the chondro-lineage. Kii, I., Amizuka, N., Shimomura, J., Saga, Y., Kudo, A. J. Bone Miner. Res. (2004) [Pubmed]
  3. Overexpression of cadherins suppresses pulmonary metastasis of osteosarcoma in vivo. Kashima, T., Nakamura, K., Kawaguchi, J., Takanashi, M., Ishida, T., Aburatani, H., Kudo, A., Fukayama, M., Grigoriadis, A.E. Int. J. Cancer (2003) [Pubmed]
  4. N-Cadherin expression in human prostate carcinoma cell lines. An epithelial-mesenchymal transformation mediating adhesion withStromal cells. Tran, N.L., Nagle, R.B., Cress, A.E., Heimark, R.L. Am. J. Pathol. (1999) [Pubmed]
  5. A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations. Marambaud, P., Wen, P.H., Dutt, A., Shioi, J., Takashima, A., Siman, R., Robakis, N.K. Cell (2003) [Pubmed]
  6. Morphoregulatory activities of NCAM and N-cadherin can be accounted for by G protein-dependent activation of L- and N-type neuronal Ca2+ channels. Doherty, P., Ashton, S.V., Moore, S.E., Walsh, F.S. Cell (1991) [Pubmed]
  7. Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin. Hermiston, M.L., Gordon, J.I. Science (1995) [Pubmed]
  8. Neural cadherin: role in selective cell-cell adhesion. Miyatani, S., Shimamura, K., Hatta, M., Nagafuchi, A., Nose, A., Matsunaga, M., Hatta, K., Takeichi, M. Science (1989) [Pubmed]
  9. Accentuated ovariectomy-induced bone loss and altered osteogenesis in heterozygous N-cadherin null mice. Lai, C.F., Cheng, S.L., Mbalaviele, G., Donsante, C., Watkins, M., Radice, G.L., Civitelli, R. J. Bone Miner. Res. (2006) [Pubmed]
  10. Genomic structure and chromosomal mapping of the mouse N-cadherin gene. Miyatani, S., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Takeichi, M. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  11. Cadherins regulate aggregation of pancreatic beta-cells in vivo. Dahl, U., Sjødin, A., Semb, H. Development (1996) [Pubmed]
  12. N-cadherin activation substitutes for the cell contact control in cell cycle arrest and myogenic differentiation: involvement of p120 and beta-catenin. Gavard, J., Marthiens, V., Monnet, C., Lambert, M., Mège, R.M. J. Biol. Chem. (2004) [Pubmed]
  13. E- and N-cadherin differ with respect to their associated p120ctn isoforms and their ability to suppress invasive growth in pancreatic cancer cells. Seidel, B., Braeg, S., Adler, G., Wedlich, D., Menke, A. Oncogene (2004) [Pubmed]
  14. Molecular modification of N-cadherin in response to synaptic activity. Tanaka, H., Shan, W., Phillips, G.R., Arndt, K., Bozdagi, O., Shapiro, L., Huntley, G.W., Benson, D.L., Colman, D.R. Neuron (2000) [Pubmed]
  15. Expression of NCAM containing VASE in neurons can account for a developmental loss in their neurite outgrowth response to NCAM in a cellular substratum. Saffell, J.L., Walsh, F.S., Doherty, P. J. Cell Biol. (1994) [Pubmed]
  16. A cadherin-like protein in eggs and cleaving embryos of Xenopus laevis is expressed in oocytes in response to progesterone. Choi, Y.S., Sehgal, R., McCrea, P., Gumbiner, B. J. Cell Biol. (1990) [Pubmed]
  17. Migration of nerve growth cones requires detergent-resistant membranes in a spatially defined and substrate-dependent manner. Nakai, Y., Kamiguchi, H. J. Cell Biol. (2002) [Pubmed]
  18. Tyrosine-phosphorylated and nonphosphorylated sodium channel beta1 subunits are differentially localized in cardiac myocytes. Malhotra, J.D., Thyagarajan, V., Chen, C., Isom, L.L. J. Biol. Chem. (2004) [Pubmed]
  19. 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]
  20. Essential tyrosine residues for interaction of the non-receptor protein-tyrosine phosphatase PTP1B with N-cadherin. Rhee, J., Lilien, J., Balsamo, J. J. Biol. Chem. (2001) [Pubmed]
  21. 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]
  22. 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]
  23. Ultrastructural analysis of development of myocardium in calreticulin-deficient mice. Lozyk, M.D., Papp, S., Zhang, X., Nakamura, K., Michalak, M., Opas, M. BMC Dev. Biol. (2006) [Pubmed]
  24. RhoA/ROCK and Cdc42 regulate cell-cell contact and N-cadherin protein level during neurodetermination of P19 embryonal stem cells. Laplante, I., Béliveau, R., Paquin, J. J. Neurobiol. (2004) [Pubmed]
  25. Connexin43 associated with an N-cadherin-containing multiprotein complex is required for gap junction formation in NIH3T3 cells. Wei, C.J., Francis, R., Xu, X., Lo, C.W. J. Biol. Chem. (2005) [Pubmed]
  26. Adhesive subdivisions intrinsic to the epithelial somites. Horikawa, K., Radice, G., Takeichi, M., Chisaka, O. Dev. Biol. (1999) [Pubmed]
  27. Localization of the novel Xin protein to the adherens junction complex in cardiac and skeletal muscle during development. Sinn, H.W., Balsamo, J., Lilien, J., Lin, J.J. Dev. Dyn. (2002) [Pubmed]
  28. A novel type of adhering junction in an epithelioid tumorigenic rat cell culture line. Schmelz, M., Way, D.L., Borgs, P., Peitsch, W.K., Schmidt, H., Witte, M.H., Witte, C.L., Franke, W.W., Moll, R. Cell Tissue Res. (1998) [Pubmed]
  29. Structure-function analysis of cell adhesion by neural (N-) cadherin. Tamura, K., Shan, W.S., Hendrickson, W.A., Colman, D.R., Shapiro, L. Neuron (1998) [Pubmed]
  30. E-cadherin and cadherin-associated cytoplasmic proteins are expressed in murine mast cells. Tegoshi, T., Nishida, M., Ishiwata, K., Kobayashi, T., Uchiyama, F., Nabeshima, K., Nawa, Y., Arizono, N. Lab. Invest. (2000) [Pubmed]
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