N-cadherin regulates spatially polarized signals through distinct p120ctn and β-catenin-dependent signaling pathways

The spatial distribution of molecular signals within cells is crucial for cellular functions. Here, as a model to study the polarized spatial distribution of molecular activities, we used cells on micro-patterned strips of fibronectin with one end free and the other end contacting a neighboring cell. Phosphoinositide 3-kinase (PI3K) and the small GTPase Rac display greater activity at the free end, whereas myosin II light chain (MLC) and actin filaments are enriched near the intercellular junction. PI3K and Rac polarization depend specifically on the N-cadherin-p120ctn complex, whereas MLC and actin filament polarization depend on the N-cadherin-β-catenin complex. Integrins promote high PI3K/Rac activities at the free end, and the N-cadherin–p120ctn complex excludes integrin α5 at the junctions to suppress local PI3K and Rac activity. We hence conclude that N-cadherin couples with distinct effectors to polarize PI3K/Rac and MLC/actin filaments in migrating cells.