ADAM10 cleavage of N-cadherin and regulation of cell–cell adhesion and -catenin nuclear signalling
Karina Reiss, Thorsten Maretzky, Andreas Ludwig, Thomas Tousseyn, Bart de Strooper, Dieter Hartmann and Paul Saftig
Cadherins are critically involved in tissue development and tissue homeostasis. We demonstrate here that neuronal cadherin (N-cadherin) is cleaved specifically by the disintegrin and metalloproteinase ADAM10 in its ectodomain. ADAM10 is not only responsible for the constitutive, but also for the regulated, shedding of this adhesion molecule in fibroblasts and neuronal cells directly regulating the overall levels of N-cadherin expression at the cell surface. The ADAM10-induced N-cadherin cleavage resulted in changes in the adhesive behaviour of cells and also in a dramatic redistribution of -catenin from the cell surface to the cytoplasmic pool, thereby influencing the expression of -catenin target genes. Our data therefore demonstrate a crucial role of ADAM10 in the regulation of cell–cell adhesion and on -catenin signalling, leading to the conclusion that this protease constitutes a central switch in the signalling pathway from N-cadherin at the cell surface to -catenin/LEF-1-regulated gene expression in the nucleus.