CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation

• DOI: 10.1016/j.neuron.2013.06.039
• Publication Date: 2013-09-18T16:17:10Z
• Authors: Silvia De Rubeis; Emanuela Pasciuto; Ka Wan Li; Esperanza Fernández; Daniele Di Marino; Andrea Buzzi; Linnaea E. Ostroff; Eric Klann; Fried J.T. Zwartk...; Noboru H. Komiyama; Seth G.N. Grant; Christel Poujol; Daniel Choquet; Tilmann Achsel; Danielle Posthuma; August B. Smit; Claudia Bagni
• Keywords: Male; Transcription Factor; Messenger; Inbred C57BL; Transgenic; Indole Alkaloids; Mice; Fragile X Mental Retardation Protein; Aminoquinoline; Tandem Mass Spectrometry; Synaptosome; Enzyme Inhibitor; Settore BIO/13 - BIOLOGIA APPLICATA; Age Factor; Enzyme Inhibitors; Cells, Cultured; Cerebral Cortex; Chromatography; Liquid; Microscopy; 0303 health sciences; Cultured; Luminescent Protein; Age Factors; Adaptor Proteins; DNA-Binding Proteins; Mental Disorder; Aminoquinolines; Indole Alkaloid; Human; Time Factor; Cells; DNA-Binding Protein; Neuroscience(all); Dendritic Spines; Green Fluorescent Proteins; Carbazole; Carbazoles; 610; In Vitro Techniques; Transfection; Green Fluorescent Protein; EMC NIHES-04-55-01; Article; 03 medical and health sciences; Dendritic Spine; Meta-Analysis as Topic; Animals; Humans; Immunoprecipitation; Adaptor Proteins, Signal Transducing; Immunoelectron; Analysis of Variance; Protein Biosynthesi; Animal; In Vitro Technique; Adaptor Proteins, Signal Transducing; Age Factors; Aminoquinolines; Analysis of Variance; Animals; Brain-Derived Neurotrophic Factor; Carbazoles; Cells, Cultured; Cerebral Cortex; Chromatography, Liquid; DNA-Binding Proteins; Dendritic Spines; Enzyme Inhibitors; Fragile X Mental Retardation Protein; Gene Expression Regulation; Green Fluorescent Proteins; Humans; Immunoprecipitation; In Vitro Techniques; Indole Alkaloids; Luminescent Proteins; Male; Mental Disorders; Meta-Analysis as Topic; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Immunoelectron; Nerve Tissue Proteins; Neurons; Protein Biosynthesis; Pyrimidines; RNA, Messenger; Synaptosomes; Tandem Mass Spectrometry; Time Factors; Transcription Factors; Transfection; Brain-Derived Neurotrophic Factor; Signal Transducing; Neuron; Pyrimidine; Gene Expression Regulation; Nerve Tissue Protein; RNA; Chromatography, Liquid

The CYFIP1/SRA1 gene is located in a chromosomal region linked to various neurological disorders, including intellectual disability, autism, and schizophrenia. CYFIP1 plays dual role two apparently unrelated processes, inhibiting local protein synthesis favoring actin remodeling. Here, we show that brain-derived neurotrophic factor (BDNF)-driven synaptic signaling releases from the translational inhibitory complex, triggering translation of target mRNAs shifting into WAVE regulatory complex. Active Rac1 alters conformation, as demonstrated by intramolecular FRET, key changing equilibrium complexes. thus orchestrates molecular cascades, polymerization, each which necessary for correct spine morphology neurons. interactome reveals many interactors associated with brain opening new perspectives define pathways shared disabilities characterized dysmorphogenesis.