Sustained Activity of Metabotropic Glutamate Receptor: Homer, Arrestin, and Beyond

• Published in: Journal of neural transplantation & plasticity 2017-01, Vol.2017 (2017), p.1-9
• Main Authors: Chung, Geehoon, Kim, Sang-Jeong
• Format: Article
• Language: English
• Subjects: Animals; beta-Arrestins - metabolism; Brain - metabolism; Cellular signal transduction; High temperature; Homer Scaffolding Proteins - metabolism; Humans; Kinases; Membrane proteins; Metabotropic glutamate receptors; Models, Neurological; Nervous system; Neurological research; Neurons; Neurons - metabolism; Phosphorylation; Physiological aspects; Physiology; Proteins; Receptors, Metabotropic Glutamate - metabolism; Review; Signal Transduction; Synapses
• ISSN: 2090-5904; 0792-8483; 1687-5443
• DOI: 10.1155/2017/5125624

When activated, metabotropic glutamate receptors (mGlus) exert long-lasting changes within the glutamatergic synapses. One mechanism is a tonic effect of downstream signal transduction pathways via sustained activation of mGlu itself. Like many other G protein-coupled receptors (GPCRs), mGlu can exist in a constitutively active state, which persists agonist independently. In this paper, we review the current knowledge of the mechanisms underlying the constitutive activity of group I mGlus. The issues concerning Homer1a mechanism in the constitutive activity of group I mGlus and recent findings regarding the significant role of β-arrestin in sustained GPCR activity are also discussed. We propose that once in a state of sustained activation, the mGlu persistently activates downstream signaling pathways, including various adaptor proteins and kinases, such as β-arrestin and mitogen-activated protein kinases. In turn, these effector molecules bind to or phosphorylate the mGlu C-terminal binding domains and consequently regulate the activation state of the mGlu.