Roles of CREB in the regulation of FMRP by group i metabotropic glutamate receptors in cingulate cortex

Hansen Wang, Yoshikazu Morishita, Daiki Miura, Jose R. Naranjo, Satoshi Kida, Min Zhuo

Research output: Contribution to journalReview articlepeer-review

17 Citations (Scopus)

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. Conclusion: 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.

Original languageEnglish
Article number27
JournalMolecular brain
Volume5
Issue number1
DOIs
Publication statusPublished - 2012

Keywords

  • CREB
  • Cingulate cortex
  • FMRP
  • Fragile X syndrome
  • Gene expression
  • Group I mGluRs

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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