A Noncanonical Postsynaptic Transport Route for a GPCR Belonging to the Serotonin Receptor Family

Abstract

Postsynaptic receptor trafficking plays an essential role in tuning neurotransmission and signal plasticity and has emerged as a potential therapeutic target in neuropsychiatric disease. Using a novel application of fluorescence recovery after photobleaching in rat hippocampal neurons, we examined transport from the soma to dendrites of seven G-protein-coupled receptors (GPCRs) implicated in mood disorders. Most GPCRs were delivered to dendrites via lateral diffusion, but one GPCR, the serotonin 1B receptor (5-HT(1B)), was delivered to the dendrites in secretory vesicles. Within the dendrites, 5-HT(1B) were stored in a reservoir of accessible vesicles that were recruited to preferential sites in plasma membrane, as observed with superecliptic pHluorin labeling. After membrane recruitment, 5-HT(1B) transport via lateral diffusion and temporal confinement to inhibitory and excitatory synapses was monitored by single particle tracking. These results suggest an alternative mechanism for control of neuronal activity via a GPCR that has been implicated in mood regulation.