文章基本信息

标题：GABAB receptor upregulates fragile X mental retardation protein expression in neurons
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作者：Wenhua Zhang ; Chanjuan Xu ; Haijun Tu 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
期号：1
DOI：10.1038/srep10468
语种：English
出版社：Springer Nature
摘要：Fragile X mental retardation protein (FMRP) is an RNA-binding protein important for the control of translation and synaptic function. The mutation or silencing of FMRP causes Fragile X syndrome (FXS), which leads to intellectual disability and social impairment. γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter of the mammalian central nervous system, and its metabotropic GABA_B receptor has been implicated in various mental disorders. The GABA_B receptor agonist baclofen has been shown to improve FXS symptoms in a mouse model and in human patients, but the signaling events linking the GABA_B receptor and FMRP are unknown. In this study, we found that GABA_B receptor activation upregulated cAMP response element binding protein-dependent Fmrp expression in cultured mouse cerebellar granule neurons via two distinct mechanisms: the transactivation of insulin-like growth factor-1 receptor and activation of protein kinase C. In addition, a positive allosteric modulator of the GABA_B receptor, CGP7930, stimulated Fmrp expression in neurons. These results suggest a role for GABA_B receptor in Fmrp regulation and a potential interest of GABA_B receptor signaling in FXS improvement.