title: Roles of CREB in the regulation of FMRP by group I metabotropic glutamate receptors in cingulate cortex.
abstract: BACKGROUND
  Fragile X syndrome is caused by lack of fragile X mental retardation protein (FMRP) due to silencing of the FMR1 gene. The metabotropic glutamate receptors (mGluRs) in the central nervous system contribute to higher brain functions including learning/memory, mental disorders and persistent pain. The transcription factor cyclic AMP-responsive element binding protein (CREB) is involved in important neuronal functions, such as synaptic plasticity and neuronal survival. Our recent study has shown that stimulation of Group I mGluRs upregulated FMRP and activated CREB in anterior cingulate cortex (ACC), a key region for brain cognitive and executive functions, suggesting that activation of Group I mGluRs may upregulate FMRP through CREB signaling pathway.
  
  
  RESULTS
  In this study, we demonstrate that CREB contributes to the regulation of FMRP by Group I mGluRs. In ACC neurons of adult mice overexpressing dominant active CREB mutant, the upregulation of FMRP by stimulating Group I mGluR is enhanced compared to wild-type mice. However, the regulation of FMRP by Group I mGluRs is not altered by overexpression of Ca2+-insensitive mutant form of downstream regulatory element antagonist modulator (DREAM), a transcriptional repressor involved in synaptic transmission and plasticity.
  
  
  CONCLUSIONS
  Our study has provided further evidence for CREB involvement in regulation of FMRP by Group I mGluRs in ACC neurons, and may help to elucidate the pathogenesis of fragile X syndrome.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
authors.forename: Hansen
authors.initials: H
authors.lastname: Wang
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Morishita
authors.forename: Daiki
authors.initials: D
authors.lastname: Miura
authors.forename: Jose R
authors.initials: JR
authors.lastname: Naranjo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kida
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
mesh_terms: D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D005799:Genes, Dominant; D006179:Gyrus Cinguli / Q000378:metabolism*; D051605:Kv Channel-Interacting Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation
chemical_list: D002118:Calcium; D017362:Cyclic AMP Response Element-Binding Protein; D051860:Fragile X Messenger Ribonucleoprotein 1; D051605:Kv Channel-Interacting Proteins; D018094:Receptors, Metabotropic Glutamate; D012097:Repressor Proteins; C492004:Creb1 protein, mouse; C496756:Csen protein, mouse; C497684:Fmr1 protein, mouse; C104077:metabotropic glutamate receptor type 1