Cadherin-Mediated Transmembrane Interactions

Abstract

We show in this study that cadherin ligands, either soluble or immobilized on different surfaces, can bind to cells carrying a compatible cadherin and induce long-range signals which affect cell adhesion and dynamics. Addition of recombinant N-cadherin extracellular domain (NEC) to CHO cells expressing N-cadherin (FL4) greatly enhanced the calcium-dependent aggregation of the cells and blocked their migration into an “in vitro wound”. Monoclonal antibody which blocks cadherin interactions inhibited the aggregation of suspended FL4 cells and facilitated the “wound closure”. As previously shown (Levenberg et al., 1998) synthetic beads coupled to NEC interacted specifically with the surface of FL4 cells and significantly enhanced the formation of adherens junctions. This effect was obtained also with the parental CHO cells, which contain low levels of N-cadherin, and in additional N-cadherin expressing cells such as cultured myoblasts. We further show here that stimulation of adhesion is not affected by the geometry of the NEC-bound surface and that cells plated on flat NEC-coated substratum also develop enhanced adherens junctions. Interaction of cells expressing low levels of endogenous N-cadherin, such as CHO cells with surface-immobilized N-cadherin ligands had a prominent effect also on the total level of N-cadherin and β-catenin in the cells, probably due to stabilization of the cadherin-catenin complex by the interaction with the external surface.

Key Words:

• Cadherin
• cell adhesion
• cytoskeleton
• signaling