Fig. 1

Schematic representation of the N-cadherin-catenin adhesive complex. The extracellular domains of N-cadherin monomers engage in trans and cis interactions with partner monomers, facilitated by p120-catenin (p120), resulting in a lattice-like arrangement. Interaction between monomers on opposing cells occurs via a reciprocal insertion of tryptophan side-chains (W) on the first extracellular domain (EC1) (trans adhesion). Clustering of N-cadherin monomers on the same cell occurs via a His-Ala-Val (HAV) adhesion motif on EC1 and a recognition sequence on the second extracellular domain (EC2) of the partner monomer (cis adhesion) (inset). Activation of RhoA sequesters β-catenin (β-cat) and results in accumulation of α-catenin (α-cat) to the N-cadherin intracellular domain. This promotes anchorage of the N-cadherin-catenin complex to the actin cytoskeleton via actin-binding proteins, thereby stabilising cell-cell contacts. Initial ligation of N-cadherin extracellular domains also triggers PI3K/Akt signalling which inactivates the pro-apoptotic protein Bad, resulting in activation of the anti-apoptotic protein Bcl-2