title: FXR2P Exerts a Positive Translational Control and Is Required for the Activity-Dependent Increase of PSD95 Expression.
abstract: In brain, specific RNA-binding proteins (RBPs) associate with localized mRNAs and function as regulators of protein synthesis at synapses exerting an indirect control on neuronal activity. Thus, the Fragile X Mental Retardation protein (FMRP) regulates expression of the scaffolding postsynaptic density protein PSD95, but the mode of control appears to be different from other FMRP target mRNAs. Here, we show that the fragile X mental retardation-related protein 2 (FXR2P) cooperates with FMRP in binding to the 3'-UTR of mouse PSD95/Dlg4 mRNA. Absence of FXR2P leads to decreased translation of PSD95/Dlg4 mRNA in the hippocampus, implying a role for FXR2P as translation activator. Remarkably, mGluR-dependent increase of PSD95 synthesis is abolished in neurons lacking Fxr2. Together, these findings show a coordinated regulation of PSD95/Dlg4 mRNA by FMRP and FXR2P that ultimately affects its fine-tuning during synaptic activity.
authors.affiliation: KU Leuven, Center for Human Genetics and Leuven Institute for Neuroscience and Disease, Leuven, Belgium, VIB Center for the Biology of Disease, 3000 Leuven, Belgium.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Fernández
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, 1081 HV Amsterdam, The Netherlands, and.
authors.forename: Ka Wan
authors.initials: KW
authors.lastname: Li
authors.affiliation: KU Leuven, Center for Human Genetics and Leuven Institute for Neuroscience and Disease, Leuven, Belgium, VIB Center for the Biology of Disease, 3000 Leuven, Belgium.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Rajan
authors.affiliation: KU Leuven, Center for Human Genetics and Leuven Institute for Neuroscience and Disease, Leuven, Belgium, VIB Center for the Biology of Disease, 3000 Leuven, Belgium.
authors.forename: Silvia
authors.initials: S
authors.lastname: De Rubeis
authors.affiliation: KU Leuven, Center for Human Genetics and Leuven Institute for Neuroscience and Disease, Leuven, Belgium, VIB Center for the Biology of Disease, 3000 Leuven, Belgium.
authors.forename: Mark
authors.identifier: http://orcid.org/0000-0001-5694-2409
authors.initials: M
authors.lastname: Fiers
authors.affiliation: Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam, 1081 HV Amsterdam, The Netherlands, and.
authors.forename: August B
authors.initials: AB
authors.lastname: Smit
authors.affiliation: KU Leuven, Center for Human Genetics and Leuven Institute for Neuroscience and Disease, Leuven, Belgium, VIB Center for the Biology of Disease, 3000 Leuven, Belgium.
authors.forename: Tilmann
authors.initials: T
authors.lastname: Achsel
authors.affiliation: KU Leuven, Center for Human Genetics and Leuven Institute for Neuroscience and Disease, Leuven, Belgium, VIB Center for the Biology of Disease, 3000 Leuven, Belgium, University of Rome Tor Vergata, Department of Biomedicine and Prevention, 00133 Rome, Italy claudia.bagni@cme.vib-kuleuven.be claudia.bagni@uniroma2.it.
authors.forename: Claudia
authors.identifier: http://orcid.org/0000-0002-4419-210X
authors.initials: C
authors.lastname: Bagni
mesh_terms: D000818:Animals; D015153:Blotting, Western; D000076122:Disks Large Homolog 4 Protein; D005786:Gene Expression Regulation / Q000502:physiology*; D051528:Guanylate Kinases / Q000096:biosynthesis* / Q000235:genetics; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D014176:Protein Biosynthesis / Q000502:physiology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; C512309:FXR2 protein, mouse; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D051528:Guanylate Kinases
keywords: FMRP; FXR2P; PSD95; RNA binding proteins; mRNA translation