Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Frans van RoyEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_39


Historical Background: The Larger Cadherin Superfamily

Cadherins comprise a large protein superfamily of calcium-dependent proteins associated with the plasma membrane. They are hallmarked by at least two consecutive extracellular cadherin repeats (ECs) in their extracellular domain. Epithelial cadherin (E-cadherin or cadherin-1) is the founding family member and represents the classic or type-I cadherins. These cadherins mediate specific and strong cell-cell adhesion and play key roles in local organization of cytoskeletal structures and in signaling cascades, as documented below. The mature E-cadherin contains an ectodomain of about 550 amino acids (AA) comprising five ECs, a single transmembrane (TM) domain, and a cytoplasmic domain (CD) of about 150 AA. The CD has two highly conserved domains for binding either p120ctn and related protein family members or β-catenin and the...
This is a preview of subscription content, log in to check access.


  1. Brigidi GS, Bamji SX. Cadherin-catenin adhesion complexes at the synapse. Curr Opin Neurobiol. 2011;21:208–14.PubMedCrossRefGoogle Scholar
  2. Casagolda D, Del Valle-Perez B, Valls G, Lugilde E, Vinyoles M, Casado-Vela J, et al. A p120-catenin-CK1epsilon complex regulates Wnt signaling. J Cell Sci. 2010;123:2621–31.PubMedCrossRefGoogle Scholar
  3. Chen B, Brinkmann K, Chen Z, Pak CW, Liao Y, Shi S, et al. The WAVE regulatory complex links diverse receptors to the actin cytoskeleton. Cell. 2014;156:195–207.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Cooper SR, Emond MR, Duy PQ, Liebau BG, Wolman MA, Jontes JD. Protocadherins control the modular assembly of neuronal columns in the zebrafish optic tectum. J Cell Biol. 2015;211:807–14.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Giampietro C, Taddei A, Corada M, Sarra-Ferraris GM, Alcalay M, Cavallaro U, et al. Overlapping and divergent signaling pathways of N-cadherin and VE-cadherin in endothelial cells. Blood. 2012;119:2159–70.PubMedCrossRefGoogle Scholar
  6. Gray RS, Roszko I, Solnica-Krezel L. Planar cell polarity: coordinating morphogenetic cell behaviors with embryonic polarity. Dev Cell. 2011;21:120–33.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Gumbiner BM. Regulation of cadherin-mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol. 2005;6:622–34.PubMedCrossRefGoogle Scholar
  8. Halbleib JM, Nelson WJ. Cadherins in development: cell adhesion, sorting, and tissue morphogenesis. Genes Dev. 2006;20:3199–214.PubMedCrossRefGoogle Scholar
  9. Harris TJ, Tepass U. Adherens junctions: from molecules to morphogenesis. Nat Rev Mol Cell Biol. 2010;11:502–14.PubMedCrossRefGoogle Scholar
  10. Hayashi S, Takeichi M. Emerging roles of protocadherins: from self-avoidance to enhancement of motility. J Cell Sci. 2015;128:1455–64.PubMedCrossRefGoogle Scholar
  11. Hoshino T, Sakisaka T, Baba T, Yamada T, Kimura T, Takai Y. Regulation of E-cadherin endocytosis by nectin through afadin, Rap1, and p120ctn. J Biol Chem. 2005;280:24095–103.PubMedCrossRefGoogle Scholar
  12. Hulpiau P, van Roy F. New insights into the evolution of metazoan cadherins. Mol Biol Evol. 2011;28:647–57.PubMedCrossRefGoogle Scholar
  13. Kooistra MRH, Dube N, Bos JL. Rap1: a key regulator in cell-cell junction formation. J Cell Sci. 2007;120:17–22.PubMedCrossRefGoogle Scholar
  14. le Duc Q, Shi QM, Blonk I, Sonnenberg A, Wang N, Leckband D, et al. Vinculin potentiates E-cadherin mechanosensing and is recruited to actin-anchored sites within adherens junctions in a myosin II-dependent manner. J Cell Biol. 2010;189:1107–15.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Lecuit T, Yap AS. E-cadherin junctions as active mechanical integrators in tissue dynamics. Nat Cell Biol. 2015;17:533–9.PubMedCrossRefGoogle Scholar
  16. Lee SH, Peng IF, Ng YG, Yanagisawa M, Bamji SX, Elia LP, et al. Synapses are regulated by the cytoplasmic tyrosine kinase Fer in a pathway mediated by p120catenin, Fer, SHP-2, and beta-catenin. J Cell Biol. 2008;183:893–908.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Nelson WJ, Fuchs E, editors. Cell-cell junctions. Cold spring harbor perspectives in biology. Woodbury: Cold Spring Harbor Laboratory Press; 2010. p. 1–443. isbn:978-0-87969-884-3.Google Scholar
  18. Niessen CM, Leckband D, Yap AS. Tissue organization by cadherin adhesion molecules: dynamic molecular and cellular mechanisms of morphogenetic regulation. Physiol Rev. 2011;91:691–731.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Pieters T, van Hengel J, van Roy F. Functions of p120ctn in development and disease. Front Biosci. 2012a;17:760–83.CrossRefGoogle Scholar
  20. Pieters T, van Roy F, van Hengel J. Functions of p120ctn isoforms in cell-cell adhesion and intracellular signaling. Front Biosci. 2012b;17:1669–94.CrossRefGoogle Scholar
  21. Sopko R, McNeill H. The skinny on Fat: an enormous cadherin that regulates cell adhesion, tissue growth, and planar cell polarity. Curr Opin Cell Biol. 2009;21:717–23.PubMedCrossRefGoogle Scholar
  22. Suzuki S, Hirano S, editors. The Cadherin superfamily – key regulators of animal development and physiology. Tokyo: Springer; 2016. 428 pages. isbn:978-4-431-56031-9.Google Scholar
  23. Takeichi M. Dynamic contacts: rearranging adherens junctions to drive epithelial remodelling. Nat Rev Mol Cell Biol. 2014;15:397–410.PubMedCrossRefGoogle Scholar
  24. Tsukasaki Y, Miyazaki N, Matsumoto A, Nagae S, Yonemura S, Tanoue T, et al. Giant cadherins Fat and Dachsous self-bend to organize properly spaced intercellular junctions. Proc Natl Acad Sci USA. 2014;111:16011–6.PubMedPubMedCentralCrossRefGoogle Scholar
  25. van Roy F, Berx G. The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci. 2008;65:3756–88.PubMedCrossRefGoogle Scholar
  26. van Roy F, editor. The molecular biology of cadherins. Progress in molecular biology and translational science, vol. 116. Burlington: Academic/Elsevier; 2013. 465 pages. isbn:978-0-12-394311-8.Google Scholar
  27. van Roy F. Beyond E-cadherin: roles of other cadherin superfamily members in cancer. Nat Rev Cancer. 2014;14:121–34.PubMedCrossRefGoogle Scholar
  28. Yonemura S, Wada Y, Watanabe T, Nagafuchi A, Shibata M. Alpha-catenin as a tension transducer that induces adherens junction development. Nat Cell Biol. 2010;12:533–42.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Molecular Cell Biology Unit, Department of Biomedical Molecular BiologyGhent University and Inflammation Research Center, VIBGhentBelgium