title: GABAB receptor upregulates fragile X mental retardation protein expression in neurons.
abstract: 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 GABAB receptor has been implicated in various mental disorders. The GABAB receptor agonist baclofen has been shown to improve FXS symptoms in a mouse model and in human patients, but the signaling events linking the GABAB receptor and FMRP are unknown. In this study, we found that GABAB 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 GABAB receptor, CGP7930, stimulated Fmrp expression in neurons. These results suggest a role for GABAB receptor in Fmrp regulation and a potential interest of GABAB receptor signaling in FXS improvement.
authors.affiliation: Cellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology and the Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Cellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology and the Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Xu
authors.affiliation: Cellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology and the Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Tu
authors.affiliation: Cellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology and the Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Cellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology and the Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Cellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology and the Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Hu
authors.affiliation: Cellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology and the Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yongjian
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Institut de Génomique Fonctionnelle, CNRS UMR5203, INSERM U1191, Université de Montpellier, Montpellier, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rondard
authors.affiliation: Cellular Signaling Laboratory, Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology and the Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D001418:Baclofen / Q000008:administration & dosage; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000096:biosynthesis* / Q000235:genetics; D005600:Fragile X Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018080:Receptors, GABA-B / Q000096:biosynthesis / Q000235:genetics*; D017451:Receptors, Somatomedin / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000235:genetics* / Q000378:metabolism
chemical_list: D001418:Baclofen; D051860:Fragile X Messenger Ribonucleoprotein 1; D018080:Receptors, GABA-B; D017451:Receptors, Somatomedin; D005680:gamma-Aminobutyric Acid