Metabotropic glutamate receptor trafficking

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The metabotropic glutamate receptors (mGlu receptors) are G protein-coupled receptors that bind to the excitatory neurotransmitter glutamate and are important in the modulation of neuronal excitability, synaptic transmission, and plasticity in the central nervous system. Trafficking of mGlu receptors in and out of the synaptic plasma membrane is a fundamental mechanism modulating excitatory synaptic function through regulation of receptor abundance, desensitization, and signaling profiles. In this review, we cover the regulatory mechanisms determining surface expression and endocytosis of mGlu receptors, with particular focus on post-translational modifications and receptor-protein interactions. The literature we review broadens our insight into the precise events defining the expression of functional mGlu receptors at synapses, and will likely contribute to the successful development of novel therapeutic targets for a variety of developmental, neurological, and psychiatric disorders.HighlightsMetabotropic glutamate receptors (mGlu receptors) undergo constitutive and agonist-induced endocytosis.The endocytosis of mGlu receptors is regulated by receptor phosphorylation and protein-protein interactions.Many proteins involved in mGlu receptor trafficking bind to the intracellular C-terminus or loop domains of mGlu receptors.The intracellular trafficking pathways of mGlu receptors are remarkably diverse.

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