Role of post synaptic scaffolding proteins picki and tamalin in group i matabotropic glutamate receptor trafficking

Abstract

G-protein-coupled receptors (GPCRs) are seven transmembrane receptors that transduce newlineinformation provided by the extracellular stimuli into intracellular signals via their coupling newlineto G-proteins. Activation of GPCR also triggers a variety of cellular and molecular newlinemechanisms, viz., receptor desensitization and internalization. Due to the diversity in the newlineGPCR regulation, each GPCR is unique and an extensively studied GPCR may not provide newlineall the details about other GPCRs. Glutamate is a major excitatory neurotransmitter in the newlinecentral nervous system. It activates three types of receptors, viz., NMDARs, AMPARs and newlinemetabotropic glutamate receptors (mGluRs). Among these three types of receptors, mGluRs newlinebelong to the GPCR family. Group I mGluR family consists of mGluR1 and mGluR5. These newlinereceptors play important roles in the brain and are believed to be involved in multiple forms newlineof experience dependent synaptic plasticity including learning and memory. In addition, newlinegroup I mGluRs also have been implicated in various neuropsychiatric disorders like Fragile newlineX syndrome, autism etc. Similar to many other GPCRs, group I mGluRs have been reported newlineto get desensitized subsequent to the ligand exposure and undergo rapid internalization. newlineThese receptors are localized in a protein dense region at the post-synaptic membrane called newlinepost-synaptic density (PSD). The post-synaptic density of excitatory synapses is very newlinecomplex in composition and dynamic in nature. This region contains a large number of newlinedifferent kinds of proteins, some of which are involved in cognitive function and have been newlineimplicated in various psychiatric disorders. The involvement of post-synaptic density proteins newlinein the ligand-mediated trafficking of group I mGluRs is relatively an unexplored area. The newlineobjective of this study is to investigate the role of post-synaptic scaffolding proteins PICK1 newlineand Tamalin in the ligand-mediated trafficking of group I mGluRs and its implications in the newlinebrain. newline