Communication between nerves and mast cells is a prototypic demonstration of neuro-immune interaction. Numerous studies have shown that the stimulation of nerves (or addition of neurotransmitters) can evoke activation of mast cells, and that mast cell-derived mediators can influence neuronal activity. However, the molecules involved in the membrane-membrane contacts between nerves and mast cells are still unknown. Here, we used an in vitro co-culture approach comprising interaction between immune (bone marrow-derived mast cell, BMMC) and nerve cells (superior cervical ganglia, SCG). The experiments showed clearly that the nerve-mast cell communication was supported by synapse-like structure and that N-cadherin, not E-cadherin, played an essential role in the synapse-like structure. In addition, we found that the synapse-like structure was assisted by clustering of β-catenin to N-cadherin.