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Soluble N‐cadherin stimulates fibroblast growth factor receptor dependent neurite outgrowth and N‐cadherin and the fibroblast growth factor receptor co‐cluster in cells

A chimeric molecule consisting of the extracellular domain of the adhesion molecule, N‐cadherin, fused to the Fc region of human IgG (NCAD‐Fc) supports calcium‐dependent cell adhesion and promotes neurite outgrowth following affinity‐capture to a tissue culture substrate. When presented to cerebellar neurons as a soluble molecule, the NCAD‐Fc stimulated neurite outgrowth in a manner equivalent to that seen for N‐cadherin expressed as a cell surface glycoprotein. Neurons expressing a dominant‐negative version of the fibroblast growth factor (FGF) receptor did not respond to soluble NCAD‐Fc. In cells transfected with full‐length N‐cadherin and the FGF receptor, antibody‐clustering of N‐cadherin resulted in a co‐clustering of the FGF receptor to discrete patches in the cell membrane. The data demonstrate that the ability of N‐cadherin to stimulate neurite outgrowth can be dissociated from its ability to function as a substrate associated adhesion molecule. The N‐cadherin and the FGF receptor co‐clustering in cells provides a basis for the neurite outgrowth response stimulated by N‐cadherin being dependent on FGF receptor function.