Role of ubiquitination in ligand-mediated trafficking of Group I Metabotropic Glutamate Receptors

Abstract

Group I metabotropic glutamate receptors (Group I mGluRs) are G protein-coupled receptors (GPCRs), that trigger various signal transduction pathways. Group I mGluRs having widespread distributions in the brain have been reported to be in- volved in various forms of synaptic plasticity, including learning behavior and memory formation. Proper trafficking of these receptors play a crucial role in regulating their functions and localization. Misregulation of these receptors has been reported to cause various neuropsychiatric disorders like fragile X syndrome, schizophrenia, autism etc. Various post-translational modifications such as ubiquitination play critical role in the ligand-mediated endocytosis of group I mGluRs. Subsequent to internalization, the majority of the receptors enter the recycling compartment and return to the cell membrane. Here, we show that deubiquitination is involved in the recycling of group I mGluRs. We further report here that, USP19 (Ubiquitin specific peptidase 19), a specific deubiquitinase (DUB) for mGluR1 plays the critical role in the recycling of the receptor.