Phosphorylation of group I metabotropic glutamate receptors (mGluR1/5) in vitro and in vivo.
Group I metabotropic glutamate receptors (mGluR1 and mGluR5 subtypes) are densely expressed in mammalian brain. They are actively involved in the regulation of normal cellular activity and synaptic plasticity, and are frequently linked to the pathogenesis of various mental illnesses. Like ionotropic glutamate receptors, group I mGluRs are subject to the regulation by protein phosphorylation. Accumulative data demonstrate sufficient phosphorylation of the intracellular mGluR1/5 domains at specific serine/threonine sites by protein kinase C in heterologous cells or neurons, which serves as an important mechanism for regulating the receptor signaling and desensitization. Emerging evidence also shows the significant involvements of G protein-coupled receptor kinases, Ca2+/calmodulin-dependent protein kinase II, tyrosine kinases, and protein phosphatases in controlling the phosphorylation status of group I mGluRs. This review analyzes the recent data concerning group I mGluR phosphorylation and the phosphorylation-dependent regulation of group I mGluR function. Future research directions in this area with newly available high throughput and proteomic approaches are also discussed in the end.
Mao
Li-Min
LM
Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, USA.
Liu
Xian-Yu
XY
Zhang
Guo-Chi
GC
Chu
Xiang-Ping
XP
Fibuch
Eugene E
EE
Wang
Lucy S
LS
Liu
Zhenguo
Z
Wang
John Q
JQ
D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D010766:Phosphorylation; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*
C578935:GRM5 protein, human; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1