Differential effects of protein phosphatases in the recycling of metabotropic glutamate receptor 5. (15th October 2015)

• Record Type: Journal Article
• Authors: Mahato, P.K.; Pandey, S.; Bhattacharyya, S.
• Is Part Of: Neuroscience. Volume 306(2015)
• Page Start: 138
• Page End: 150
• Publication Date: 2015-10-15
• Subjects: ANOVA analysis of variance -- DHPG 3, 5-Dihydroxyphenylglycine -- DMEM Dulbecco's modified Eagle's medium -- GPCRs G-protein coupled receptors -- mGluRs metabotropic glutamate receptors -- NGS Normal Goat Serum -- PFA paraformaldehyde -- PP2A protein phosphatase 2A -- PP2B protein phosphatase 2B; endocytosis -- trafficking -- receptor recycling -- GPCR -- metabotropic glutamate receptors -- neurotransmitter receptors; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.08.031
• Languages: English
• ISSNs: 0306-4522

Abstract

Graphical abstract: Highlights: mGluR5 recycles to the cell membrane after ligand-dependent endocytosis. Recycling of mGluR5 is completely PP2A-dependent. Inhibition of PP2B partially inhibits the recycling of mGluR5. Abstract: The major excitatory neurotransmitter Glutamate acts on both ionotropic and metabotropic glutamate receptors (mGluRs) in the central nervous system. mGluR5, a member of the group I mGluR family is widely expressed throughout the brain and plays important roles in a variety of neuronal processes including various forms of synaptic plasticity. This receptor is also involved in various neuropsychiatric disorders, viz., Fragile X syndrome, autism etc. It has been reported that mGluR5 undergoes desensitization and subsequently internalization on ligand exposure in various cell types. However, the downstream events after the internalization and the molecular players involved in the post-endocytic events of this receptor have not been studied. In the present study, we find that subsequent to internalization mGluR5 enters the recycling compartment. After that the receptor recycles back to the cell surface. We also show here that the recycling of mGluR5 is dependent on protein phosphatases. Our data suggest that mGluR5 recycling is completely dependent on the activity of PP2A whereas, PP2B has partial effect on this process. Thus our study suggests that mGluR5 recycles back to the cell surface after ligand-dependent internalization and protein phosphatases that have been implicated in various forms of synaptic plasticity have differential effects on the recycling of mGluR5.