| First Author | Wang H | Year | 2009 |
| Journal | J Biol Chem | Volume | 284 |
| Issue | 28 | Pages | 18953-62 |
| PubMed ID | 19436069 | Mgi Jnum | J:151259 |
| Mgi Id | MGI:4353468 | Doi | 10.1074/jbc.M109.019141 |
| Citation | Wang H, et al. (2009) Ca2+/calmodulin-dependent protein kinase IV links group I metabotropic glutamate receptors to fragile X mental retardation protein in cingulate cortex. J Biol Chem 284(28):18953-62 |
| abstractText | Fragile X syndrome is caused by a 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, persistent pain, and mental disorders. Our recent study has shown that activation of Group I mGluR up-regulated FMRP in anterior cingulate cortex (ACC), a key region for brain cognitive and executive functions; Ca(2+) signaling pathways could be involved in the regulation of FMRP by Group I mGluRs. In this study we demonstrate that stimulating Group I mGluRs activates Ca(2+)/calmodulin-dependent protein kinase IV (CaMKIV) in ACC neurons. In ACC neurons of adult mice overexpressing CaMKIV, the up-regulation of FMRP by stimulating Group I mGluR is enhanced. The enhancement occurs at the transcriptional level as the Fmr1 mRNA level was further elevated compared with wild-type mice. Using pharmacological approaches, we found that inhibition of CaMKIV could attenuate the up-regulation of FMRP by Group I mGluRs. CaMKIV contribute to the regulation of FMRP by Group I mGluRs probably through cyclic AMP-responsive element binding protein (CREB) activation, as manipulation of CaMKIV could simultaneously cause the change of CREB phosphorylation induced by Group I mGluR activation. Our study has provided strong evidence for CaMKIV as a molecular link between Group I mGluRs and FMRP in ACC neurons and may help us to elucidate the pathogenesis of fragile X syndrome. |
