title: Glutamate signaling to Ras-MAPK in striatal neurons: mechanisms for inducible gene expression and plasticity.
abstract: Extracellular signals can regulate mitogen-activated protein kinase (MAPK) cascades through a receptor-mediated mechanism in postmitotic neurons of adult mammalian brain. Both ionotropic and metabotropic glutamate receptors (mGluRs) are found to possess such an ability in striatal neurons. NMDA and AMPA receptor signals seem to share a largely common route to MAPK phosphorylation which involves first activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) via Ca2+ influx, followed by subsequent induction of phosphoinositide 3-kinase (PI3-kinase). Through its lipid and protein kinase activity, active PI3-kinase may transduce signals to Ras-MAPK cascades via at least two distinct pathways. A novel, Ca(2+)-independent pathway is believed to mediate mGluR signals to Ras-MAPK activation. As an information superhighway between the surface membrane and the nucleus, Ras-MAPK cascades, through activating their specific nuclear transcription factor targets, are actively involved in the regulation of gene expression. Emerging evidence shows that MAPK-mediated genomic responses in striatal neurons to drug exposure contribute to the development of neuroplasticity related to addictive properties of drugs of abuse.
authors.affiliation: Department of Pharmacology, University of Missouri-Kansas City, Kansas City, MO, USA. wangjq@umkc.edu
authors.forename: John Q
authors.initials: JQ
authors.lastname: Wang
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Tang
authors.forename: Nikhil K
authors.initials: NK
authors.lastname: Parelkar
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Liu
authors.forename: Shazia
authors.initials: S
authors.lastname: Samdani
authors.forename: Eun Sang
authors.initials: ES
authors.lastname: Choe
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.forename: Limin
authors.initials: L
authors.lastname: Mao
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D017072:Neostriatum / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D018631:ras Proteins / Q000378:metabolism*
chemical_list: D018698:Glutamic Acid; D018631:ras Proteins