Serotonin 2B Receptor by Interacting with NMDA Receptor and CIPP Protein Complex May Control Structural Plasticity at Glutamatergic Synapses

The serotonin 2B (5-HT2B) receptor coupled to Gq-protein contributes the control of neuronal excitability and is implicated in various psychiatric disorders. mechanisms underlying its brain function are not fully described. Using peptide affinity chromatography combined with mass spectrometry, we found that PDZ binding motif 5-HT2B located at C-terminal end interacts scaffolding protein channel interacting (CIPP). We then showed, COS-7 cells, association CIPP enhanced receptor-operated inositol phosphate (IP) production without affecting cell surface intracellular levels. Co-immunoprecipitation experiments revealed CIPP, receptor, NR1 subunit NMDA form a macromolecular complex. increased clustering primary cultured hippocampal neurons prevented dispersion following agonist stimulation, thus potentiating IP calcium mobilization dendrites. or stimulation turn dispersed clusters colocalized receptors density maturation dendritic spines. Collectively, our results suggest may signaling platform by which can influence structural plasticity excitatory glutamatergic synapses.