Metabotropic glutamate receptor internalization and synaptic AMPA receptor endocytosis by dopamine.

Abstract

Group I metabotropic glutamate receptors (mGluRs) play important roles in synaptic function, plasticity and in many neuropsychiatric disorders. Trafficking plays crucial roles in proper targeting of these receptors in specific region of the neuron and also regulating the activity of these receptors. Group I mGluRs encounter dopamine in various regions of the brain and multiple evidences suggest that dopamine might regulate these receptors in the hippocampus. We show here, dopamine induces internalization of both members of the group I mGluR family, mGluR1 and mGluR5 in hippocampal neurons derived from mice through clathrin-dependent, but dynamin-independent pathway. Dopamine increases the mGluR-mediated Gαq activity and phosphorylation of MAP kinases. Subsequent to the dopamine-mediated internalization receptors recycle to the cell surface faster than agonist-mediated internalized receptors. Recycling of the dopamine-mediated internalized mGluR1 is protein phosphatase 2B-dependent. Finally, we report that dopamine also induces the mGluR-mediated synaptic AMPA receptor endocytosis, the cellular correlate of mGluR-dependent synaptic plasticity. Thus, this study unravels a novel role for dopamine in the internalization of mGluRs and mGluR-mediated AMPA receptor endocytosis.