Group I metabotropic glutamate receptor-mediated gene expression in striatal neurons.
Group I mGluRs (mGluR1/5) are G-protein-coupled receptors and are abundantly expressed in most of medium spiny projection neurons in the striatum. Recent evidence demonstrates that group I mGluRs are among essential regulators for constitutive and inducible gene expression in host neurons. Upon activation, mGluR1/5 signals activate extracellular signal-regulated kinases (ERKs) which in turn phosphorylate transcription factors such as cAMP response element-binding protein (CREB) and Elk-1, and thereby facilitate immediate early gene and opioid peptide gene expression. The conventional mGluR1/5 signaling cascade (phosphoinositide hydrolysis and intracellular Ca(2+) release) participates in linking mGluR1/5 to ERK. Additionally, the prominent mGluR1/5 adaptor protein Homer contributes to assemble an efficient signaling apparatus connecting mGluR1/5 to gene expression. The mGluR1/5 linkage to transcription also functions in dopamine-stimulated gene expression. Together, the mGluR1/5-mediated gene expression constitutes a transcription-dependent mechanism underlying molecular adaptations and plasticity related to the pathogenesis of various mental illnesses.
Mao
Li-Min
LM
Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, 2411 Holmes Street, Kansas City, MO 64108, USA.
Zhang
Guo-Chi
GC
Liu
Xian-Yu
XY
Fibuch
Eugene E
EE
Wang
John Q
JQ
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D000072233:Homer Scaffolding Proteins; D017874:Immediate-Early Proteins / Q000502:physiology; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000096:biosynthesis*; D014157:Transcription Factors / Q000502:physiology
D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D017874:Immediate-Early Proteins; D018094:Receptors, Metabotropic Glutamate; D014157:Transcription Factors; C104077:metabotropic glutamate receptor type 1; D008734:Methoxyhydroxyphenylglycol; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; C010117:3,4-dihydroxyphenylglycol; D004298:Dopamine