Roles of calcium-stimulated adenylyl cyclase and calmodulin-dependent protein kinase IV in the regulation of FMRP by group I metabotropic glutamate receptors.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Hansen WangMin Zhuo

Abstract

The fragile X syndrome is caused by the lack of fragile X mental retardation protein (FMRP) attributable to silencing of the FMR1 gene. The metabotropic glutamate receptors (mGluRs) in the CNS contribute to different brain functions, including learning/memory, mental disorders, drug addiction, and persistent pain. Most of the previous studies have been focused on downstream targets of FMRP in hippocampal neurons, and fewer studies have been reported for the second-messenger signaling pathways between group I mGluRs and FMRP. Furthermore, no molecular study has been performed in the anterior cingulate cortex (ACC), a key region involved in high brain cognitive and executive functions. In this study, we demonstrate that activation of group I mGluR upregulated FMRP in ACC neurons of adult mice through the Ca(2+)-dependent signaling pathways. Using genetic approaches, we found that Ca(2+)/calmodulin-stimulated adenylyl cyclase 1 (AC1) and calcium/calmodulin-dependent kinase IV (CaMKIV) contribute to the upregulation of FMRP induced by stimulating group I mGluRs. The upregulation of FMRP occurs at the transcriptional level. The cAMP-dependent protein kinase is activated by stimulating group I mGluRs through AC1 in ACC neurons. Both ...Continue Reading

Citations

Jul 29, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Christina GrossGary J Bassell
Jan 14, 2011·Science Translational Medicine·Hansen WangMin Zhuo
Apr 26, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Marian T Sepulveda-OrengoJames T Porter
Jul 1, 2008·Oxidative Medicine and Cellular Longevity·Kenneth MaieseJinling Hou
Oct 25, 2011·Annual Review of Pathology·Michael R SantoroStephen T Warren
Jun 19, 2014·Proceedings of the National Academy of Sciences of the United States of America·Soledad DomínguezWashington Buño
Apr 13, 2011·Journal of Neurodevelopmental Disorders·Elizabeth Berry-KravisCrystal Hervey
Mar 3, 2015·Frontiers in Cellular Neuroscience·Hansen Wang
Mar 15, 2015·Frontiers in Cellular Neuroscience·Hansen WangLaurie C Doering
May 29, 2015·Scientific Reports·Wenhua ZhangJianfeng Liu
Apr 20, 2017·International Journal of Molecular Sciences·Oded Oron, Evan Elliott
Sep 14, 2021·Annual Review of Pharmacology and Toxicology·Khaled S Abd-Elrahman, Stephen S G Ferguson

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