The fully linked HTML version of this article has now been published.
JCS ePress
online publication date 25 Jan 2005
doi: 10.1242/jcs.01665
Research Article
The mechanism of cell adhesion by classical cadherins: the role of domain 1
Oliver J. Harrison,
Elaine M. Corps,
Torunn Berge,
and
Peter J. Kilshaw*
* Author for correspondence (e-mail: peter.kilshaw{at}bbsrc.ac.uk)
The mechanism by which classical cadherins mediate cell adhesion and, in particular, the roles played by calcium and Trp2, the second amino acid in the N-terminal domain, have long been controversial. We have used antibodies to investigate the respective contributions of Trp2 and calcium to the stability of the N-terminal domain of N-cadherin. Using a peptide antibody to the 
B strand in domain 1, which detects a disordered structure, we show that both Trp2 and calcium play crucial parts in regulating stability of the domain. The epitope for another antibody, mAb GC4, has been mapped to the base of domain 1. Binding of GC4 to this epitope was shown to depend on intramolecular 'docking' of Trp2 into the domain 1 structure. Using this property, we provide evidence that calcium regulates a dynamic equilibrium between docked and undocked Trp2. Finally, a novel technique has been developed to test whether Trp2 cross-intercalation between cadherin molecules from adjacent cells (strand exchange) is central to cadherin-mediated cell adhesion. Guided by crystal structures showing strand exchange, we have introduced single cysteine point mutations into N-cadherin domain 1 in such a way that a disulphide bond will form between opposing N-cadherin molecules during cell adhesion if strand exchange occurs. The bond requires complementary cysteines to be precisely juxtaposed according to the strand exchange model. Our results demonstrate that the disulphide bond forms as predicted. This provides compelling evidence that strand exchange is indeed a primary event in cell adhesion by classical cadherins.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
P. Pittet, K. Lee, A. J. Kulik, J.-J. Meister, and B. Hinz
Fibrogenic fibroblasts increase intercellular adhesion strength by reinforcing individual OB-cadherin bonds
J. Cell Sci.,
March 15, 2008;
121(6):
877 - 886.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-H. Chien, N. Jiang, F. Li, F. Zhang, C. Zhu, and D. Leckband
Two Stage Cadherin Kinetics Require Multiple Extracellular Domains but Not the Cytoplasmic Region
J. Biol. Chem.,
January 25, 2008;
283(4):
1848 - 1856.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Tsuiji, L. Xu, K. Schwartz, and B. M. Gumbiner
Cadherin Conformations Associated with Dimerization and Adhesion
J. Biol. Chem.,
April 27, 2007;
282(17):
12871 - 12882.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. A. Lovett, I. Gonzalez, D. A. M. Salih, L. J. Cobb, G. Tripathi, R. A. Cosgrove, A. Murrell, P. J. Kilshaw, and J. M. Pell
Convergence of Igf2 expression and adhesion signalling via RhoA and p38 MAPK enhances myogenic differentiation
J. Cell Sci.,
December 1, 2006;
119(23):
4828 - 4840.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Thoumine, M. Lambert, R.-M. Mege, and D. Choquet
Regulation of N-Cadherin Dynamics at Neuronal Contacts by Ligand Binding and Cytoskeletal Coupling
Mol. Biol. Cell,
February 1, 2006;
17(2):
862 - 875.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. J. Harrison, E. M. Corps, and P. J. Kilshaw
Cadherin adhesion depends on a salt bridge at the N-terminus
J. Cell Sci.,
September 15, 2005;
118(18):
4123 - 4130.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2005
