Protein Information

ID 2070
Name FMRP
Synonyms FMR 1; FMR1; FMRP; FRAXA; Fragile X mental retardation 1; Fragile X mental retardation 1 protein; Fragile X mental retardation syndrome protein; Protein FMR 1…

Compound Information

ID 1708
Name ACC
CAS 1-aminocyclopropanecarboxylic acid

Reference

PubMed Abstract RScore(About this table)
19436069 Wang H, Fukushima H, Kida S, Zhuo M: Ca2+/calmodulin-dependent protein kinase IV links group I metabotropic glutamate receptors to fragile X mental retardation protein in cingulate cortex. J Biol Chem. 2009 Jul 10;284(28):18953-62. Epub 2009 May 12.
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.
6(0,0,0,6)