Home LiteratureArticle Details
PMID: 17023539 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Similarities between heterophilic and homophilic cadherin adhesion.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 103 ·No. 42 ·2006-10-17 ·Pages 15434-9

Prakasam AK, Maruthamuthu V, Leckband DE

Abstract

The mechanism that drives the segregation of cells into tissue-specific subpopulations during development is largely attributed to differences in intercellular adhesion. This process requires the cadherin family of calcium-dependent glycoproteins. A widely held view is that protein-level discrimination between different cadherins on cell surfaces drives this sorting process. Despite this postulated molecular selectivity, adhesion selectivity has not been quantitatively verified at the protein level. In this work, molecular force measurements and bead aggregation assays tested whether differences in cadherin bond strengths could account for cell sorting in vivo and in vitro. Studies were conducted with chicken N-cadherin, canine E-cadherin, and Xenopus C-cadherin. Both qualitative bead aggregation and quantitative force measurements show that the cadherins cross-react. Furthermore, heterophilic adhesion is not substantially weaker than homophilic adhesion, and the measured differences in adhesion do not correlate with cell sorting behavior. These results suggest that the basis for cell segregation during morphogenesis does not map exclusively to protein-level differences in cadherin adhesion.

MeSH Terms
Animals Cadherins/metabolism Cell Line Chickens Cricetinae Dogs Humans Lipid Bilayers/chemistry Morphogenesis Protein Binding Protein Conformation Stress, Mechanical Xenopus Proteins/metabolism Xenopus laevis
Chemicals
CDH3 protein, Xenopus Cadherins Lipid Bilayers Xenopus Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Prakasam A K
Department of Chemical and Biomolecular Engineering, Center for Biophysics and Computational Biology, University of Illinois at Urbana, Urbana-Champaign, IL 61801, USA.
Maruthamuthu V
Leckband D E
References (52)
52 references, click to expand
  1. Cadherin interaction probed by atomic force microscopy.
    Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4005-10 PMID: 10759550
  2. Specificity of cell-cell adhesion by classical cadherins: Critical role for low-affinity dimerization through beta-strand swapping.
    Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8531-6 PMID: 15937105
  3. Rescuing the N-cadherin knockout by cardiac-specific expression of N- or E-cadherin.
    Development. 2001 Feb;128(4):459-69 PMID: 11171330
  4. Direct evidence that neural cell adhesion molecule (NCAM) polysialylation increases intermembrane repulsion and abrogates adhesion.
    J Biol Chem. 2005 Jan 7;280(1):137-45 PMID: 15504723
  5. C-cadherin ectodomain structure and implications for cell adhesion mechanisms.
    Science. 2002 May 17;296(5571):1308-13 PMID: 11964443
  6. Cadherin-mediated cell adhesion and tissue segregation: qualitative and quantitative determinants.
    Dev Biol. 2003 Jan 15;253(2):309-23 PMID: 12645933
  7. Analysis of heterophilic and homophilic interactions of cadherins using the c-Jun/c-Fos dimerization domains.
    J Biol Chem. 2002 May 31;277(22):19455-60 PMID: 11909859
  8. Cell sorting-out is modulated by both the specificity and amount of different cell adhesion molecules (CAMs) expressed on cell surfaces.
    Proc Natl Acad Sci U S A. 1989 Sep;86(18):7043-7 PMID: 2780560
  9. Two chick embryonic adhesion systems: molecular vs tissue specificity.
    J Supramol Struct Cell Biochem. 1981;16(1):15-27 PMID: 7299838
  10. Calcium site mutations in cadherin: impact on adhesion and evidence of cooperativity.
    Biochemistry. 2006 Jun 6;45(22):6930-9 PMID: 16734428
  11. Single-molecule analysis of cadherin-mediated cell-cell adhesion.
    J Cell Sci. 2006 Jan 1;119(Pt 1):66-74 PMID: 16371651
  12. Morphogenetic roles of classic cadherins.
    Curr Opin Cell Biol. 1995 Oct;7(5):619-27 PMID: 8573335
  13. Trans-bonded pairs of E-cadherin exhibit a remarkable hierarchy of mechanical strengths.
    Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16472-7 PMID: 15546992
  14. Direct measurements of multiple adhesive alignments and unbinding trajectories between cadherin extracellular domains.
    Biophys J. 2001 Apr;80(4):1758-68 PMID: 11259289
  15. Hydrodynamic forces applied on intercellular bonds, soluble molecules, and cell-surface receptors.
    Biophys J. 2004 Jan;86(1 Pt 1):576-88 PMID: 14695302
  16. On the mechanism of tissue reconstruction by dissociated cells. I. Population kinetics, differential adhesiveness. and the absence of directed migration.
    Proc Natl Acad Sci U S A. 1962 Sep 15;48:1577-82 PMID: 13916689
  17. Cadherins in cancer: implications for invasion and metastasis.
    Curr Opin Cell Biol. 1993 Oct;5(5):806-11 PMID: 8240824
  18. Immobilized dimers of N-cadherin-Fc chimera mimic cadherin-mediated cell contact formation: contribution of both outside-in and inside-out signals.
    J Cell Sci. 2000 Jun;113 ( Pt 12):2207-19 PMID: 10825293
  19. Regulation of cadherin-mediated adhesion in morphogenesis.
    Nat Rev Mol Cell Biol. 2005 Aug;6(8):622-34 PMID: 16025097
  20. Probabilistic modeling of shear-induced formation and breakage of doublets cross-linked by receptor-ligand bonds.
    Biophys J. 1999 Feb;76(2):1112-28 PMID: 9916043
  21. Localization of specificity determining sites in cadherin cell adhesion molecules.
    Cell. 1990 Apr 6;61(1):147-55 PMID: 2317870
  22. Ca2+ dependency of N-cadherin function probed by laser tweezer and atomic force microscopy.
    J Neurosci. 2003 Dec 3;23(35):11008-14 PMID: 14657157
  23. Multiple cadherin extracellular repeats mediate homophilic binding and adhesion.
    J Cell Biol. 2001 Jul 9;154(1):231-43 PMID: 11449003
  24. Distinct calcium-independent and calcium-dependent adhesion systems of chicken embryo cells.
    Proc Natl Acad Sci U S A. 1981 Jan;78(1):387-91 PMID: 6165990
  25. Continuous production of soluble extracellular domain of a type-I transmembrane protein in mammalian cells using an Epstein-Barr virus Ori-P-based expression vector.
    Anal Biochem. 1996 Nov 15;242(2):276-8 PMID: 8937575
  26. Conformational changes of the recombinant extracellular domain of E-cadherin upon calcium binding.
    Eur J Biochem. 1994 Aug 1;223(3):1019-26 PMID: 8055942
  27. Cadherin-mediated cell sorting not determined by binding or adhesion specificity.
    J Cell Biol. 2002 Jan 21;156(2):389-399 PMID: 11790800
  28. Mechanism of homophilic adhesion by the neural cell adhesion molecule: use of multiple domains and flexibility.
    Proc Natl Acad Sci U S A. 2004 May 4;101(18):6963-8 PMID: 15118102
  29. Dynamics of neutrophil aggregation in couette flow revealed by videomicroscopy: effect of shear rate on two-body collision efficiency and doublet lifetime.
    Biophys J. 2001 Oct;81(4):2020-34 PMID: 11566775
  30. Cell adhesion: the molecular basis of tissue architecture and morphogenesis.
    Cell. 1996 Feb 9;84(3):345-57 PMID: 8608588
  31. Engineered protein a for the orientational control of immobilized proteins.
    Bioconjug Chem. 2003 Sep-Oct;14(5):974-8 PMID: 13129401
  32. Formation of heterotypic adherens-type junctions between L-CAM-containing liver cells and A-CAM-containing lens cells.
    Cell. 1987 Sep 11;50(6):987-94 PMID: 3621349
  33. Direct measurements of forces between phosphatidylcholine and phosphatidylethanolamine bilayers in aqueous electrolyte solutions.
    Biochemistry. 1985 Aug 13;24(17):4608-18 PMID: 4063343
  34. Calcium-dependent homoassociation of E-cadherin by NMR spectroscopy: changes in mobility, conformation and mapping of contact regions.
    J Mol Biol. 2002 Dec 6;324(4):823-39 PMID: 12460580
  35. The differential adhesion hypothesis: a direct evaluation.
    Dev Biol. 2005 Feb 1;278(1):255-63 PMID: 15649477
  36. Cadherin cell adhesion receptors as a morphogenetic regulator.
    Science. 1991 Mar 22;251(5000):1451-5 PMID: 2006419
  37. Structure-function analysis of cell adhesion by neural (N-) cadherin.
    Neuron. 1998 Jun;20(6):1153-63 PMID: 9655503
  38. The binding energy of two nitrilotriacetate groups sharing a nickel ion.
    J Am Chem Soc. 2005 Mar 23;127(11):3879-84 PMID: 15771524
  39. Intermolecular forces in biology.
    Q Rev Biophys. 2001 May;34(2):105-267 PMID: 11771120
  40. Homophilic adhesion by cadherins.
    Curr Opin Struct Biol. 1999 Apr;9(2):275-81 PMID: 10322209
  41. Lifetime measurements reveal kinetic differences between homophilic cadherin bonds.
    Biophys J. 2006 Feb 15;90(4):1385-95 PMID: 16326909
  42. A new crystal structure, Ca2+ dependence and mutational analysis reveal molecular details of E-cadherin homoassociation.
    EMBO J. 1999 Apr 1;18(7):1738-47 PMID: 10202138
  43. Molecular and functional analysis of cadherin-based adherens junctions.
    Annu Rev Cell Dev Biol. 1997;13:119-46 PMID: 9442870
  44. Homophilic adhesion of E-cadherin occurs by a co-operative two-step interaction of N-terminal domains.
    EMBO J. 1996 Jul 15;15(14):3507-14 PMID: 8670853
  45. Lateral dimerization is required for the homophilic binding activity of C-cadherin.
    J Cell Biol. 1996 Oct;135(2):487-96 PMID: 8896604
  46. Structural basis of cell-cell adhesion by cadherins.
    Nature. 1995 Mar 23;374(6520):327-37 PMID: 7885471
  47. Experimental specification of cell sorting, tissue spreading, and specific spatial patterning by quantitative differences in cadherin expression.
    Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):206-9 PMID: 8278366
  48. Monte Carlo simulation of the heterotypic aggregation kinetics of platelets and neutrophils.
    Biophys J. 1999 Sep;77(3):1733-46 PMID: 10465782
  49. Direct measurements of heterotypic adhesion between the cell surface proteins CD2 and CD48.
    Biochemistry. 2002 Oct 8;41(40):12163-70 PMID: 12356317
  50. Cell sorting is analogous to phase ordering in fluids.
    Proc Natl Acad Sci U S A. 2000 Aug 15;97(17):9467-71 PMID: 10944216
  51. Direct molecular force measurements of multiple adhesive interactions between cadherin ectodomains.
    Proc Natl Acad Sci U S A. 1999 Oct 12;96(21):11820-4 PMID: 10518534
  52. Structural basis of calcium-induced E-cadherin rigidification and dimerization.
    Nature. 1996 Mar 28;380(6572):360-4 PMID: 8598933
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0606701103
Published
2006-10-17
Epub
2006-00-05
Pages
15434-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1622841
Subset
IM
Grants
NIGMS NIH HHS · R01 GM051338 · United States
NIGMS NIH HHS · 5 R01 GM51338 · United States
External Links
PubMed source DOI: 10.1073/pnas.0606701103 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2