The 5-HT4 receptor interacts with adhesion molecule L1 to modulate morphogenic signaling in neurons

Morphological remodeling of dendritic spines is critically involved in memory formation and depends on adhesion molecules. Serotonin receptors are also implicated in this remodeling, though the underlying mechanisms remain enigmatic. Here, we uncovered a signaling pathway involving the adhesion molecule L1CAM (L1) and serotonin receptor 5-HT4 (5-HT4R, encoded by HTR4). Using Forster resonance energy transfer (FRET) imaging, we demonstrated a physical interaction between 5-HT4R and L1, and found that 5-HT4R-L1 heterodimerization facilitates mitogen-activated protein kinase activation in a G(s)-dependent manner. We also found that 5-HT4R-L1-mediated signaling is involved in G(13) dependent modulation of cofilin-1 activity. In hippocampal neurons in vitro, the 5-HT4R-L1 pathway triggers maturation of dendritic spines. Thus, the 5-HT4R-L1 signaling module represents a previously unknown molecular pathway regulating synaptic remodeling.

Automated summary

The study uncovered a signaling pathway involving L1CAM and 5-HT4 receptor that facilitates dendritic spine maturation and affects memory formation.