PMID- 24050404 OWN - NLM STAT- MEDLINE DCOM- 20131113 LR - 20230919 IS - 1097-4199 (Electronic) IS - 0896-6273 (Print) IS - 0896-6273 (Linking) VI - 79 IP - 6 DP - 2013 Sep 18 TI - CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic spine formation. PG - 1169-82 LID - S0896-6273(13)00555-2 [pii] LID - 10.1016/j.neuron.2013.06.039 [doi] AB - The CYFIP1/SRA1 gene is located in a chromosomal region linked to various neurological disorders, including intellectual disability, autism, and schizophrenia. CYFIP1 plays a dual role in two apparently unrelated processes, inhibiting local protein synthesis and favoring actin remodeling. Here, we show that brain-derived neurotrophic factor (BDNF)-driven synaptic signaling releases CYFIP1 from the translational inhibitory complex, triggering translation of target mRNAs and shifting CYFIP1 into the WAVE regulatory complex. Active Rac1 alters the CYFIP1 conformation, as demonstrated by intramolecular FRET, and is key in changing the equilibrium of the two complexes. CYFIP1 thus orchestrates the two molecular cascades, protein translation and actin polymerization, each of which is necessary for correct spine morphology in neurons. The CYFIP1 interactome reveals many interactors associated with brain disorders, opening new perspectives to define regulatory pathways shared by neurological disabilities characterized by spine dysmorphogenesis. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - De Rubeis, Silvia AU - De Rubeis S AD - VIB Center for Biology of Disease, KULeuven, 3000 Leuven, Belgium; Center for Human Genetics and Leuven Institute for Neuroscience and Disease (LIND), KULeuven, 3000 Leuven, Belgium. FAU - Pasciuto, Emanuela AU - Pasciuto E FAU - Li, Ka Wan AU - Li KW FAU - Fernandez, Esperanza AU - Fernandez E FAU - Di Marino, Daniele AU - Di Marino D FAU - Buzzi, Andrea AU - Buzzi A FAU - Ostroff, Linnaea E AU - Ostroff LE FAU - Klann, Eric AU - Klann E FAU - Zwartkruis, Fried J T AU - Zwartkruis FJ FAU - Komiyama, Noboru H AU - Komiyama NH FAU - Grant, Seth G N AU - Grant SG FAU - Poujol, Christel AU - Poujol C FAU - Choquet, Daniel AU - Choquet D FAU - Achsel, Tilmann AU - Achsel T FAU - Posthuma, Danielle AU - Posthuma D FAU - Smit, August B AU - Smit AB FAU - Bagni, Claudia AU - Bagni C LA - eng GR - Wellcome Trust/United Kingdom GR - 089703/Wellcome Trust/United Kingdom GR - GGP10150/TI_/Telethon/Italy PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Neuron JT - Neuron JID - 8809320 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Aminoquinolines) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Carbazoles) RN - 0 (Cyfip1 protein, mouse) RN - 0 (DNA-Binding Proteins) RN - 0 (Elf4 protein, mouse) RN - 0 (Enzyme Inhibitors) RN - 0 (Fmr1 protein, mouse) RN - 0 (Indole Alkaloids) RN - 0 (Luminescent Proteins) RN - 0 (NCKAP1 protein, human) RN - 0 (NSC 23766) RN - 0 (Nerve Tissue Proteins) RN - 0 (Pyrimidines) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factors) RN - 0 (enhanced green fluorescent protein) RN - 139135-51-6 (Fragile X Mental Retardation Protein) RN - 147336-22-9 (Green Fluorescent Proteins) RN - 97161-97-2 (staurosporine aglycone) SB - IM MH - Adaptor Proteins, Signal Transducing/chemistry/genetics/metabolism MH - Age Factors MH - Aminoquinolines/pharmacology MH - Analysis of Variance MH - Animals MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Carbazoles/pharmacology MH - Cells, Cultured MH - Cerebral Cortex/cytology MH - Chromatography, Liquid MH - DNA-Binding Proteins/metabolism MH - Dendritic Spines/drug effects/*genetics/ultrastructure MH - Enzyme Inhibitors/pharmacology MH - Fragile X Mental Retardation Protein/genetics/metabolism/ultrastructure MH - Gene Expression Regulation/genetics MH - Green Fluorescent Proteins/genetics/metabolism MH - Humans MH - Immunoprecipitation MH - In Vitro Techniques MH - Indole Alkaloids/pharmacology MH - Luminescent Proteins/metabolism MH - Male MH - Mental Disorders/genetics MH - Meta-Analysis as Topic MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Microscopy, Immunoelectron MH - Nerve Tissue Proteins/chemistry/genetics/*metabolism/ultrastructure MH - Neurons/drug effects/*ultrastructure MH - Protein Biosynthesis/drug effects/*genetics MH - Pyrimidines/pharmacology MH - RNA, Messenger/*metabolism MH - Synaptosomes/drug effects/metabolism/ultrastructure MH - Tandem Mass Spectrometry MH - Time Factors MH - Transcription Factors/metabolism MH - Transfection PMC - PMC3781321 EDAT- 2013/09/21 06:00 MHDA- 2013/11/14 06:00 PMCR- 2013/09/18 CRDT- 2013/09/21 06:00 PHST- 2013/06/18 00:00 [accepted] PHST- 2013/09/21 06:00 [entrez] PHST- 2013/09/21 06:00 [pubmed] PHST- 2013/11/14 06:00 [medline] PHST- 2013/09/18 00:00 [pmc-release] AID - S0896-6273(13)00555-2 [pii] AID - 10.1016/j.neuron.2013.06.039 [doi] PST - ppublish SO - Neuron. 2013 Sep 18;79(6):1169-82. doi: 10.1016/j.neuron.2013.06.039.