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.

Derubeis, S., Pasciuto, E., Li, K., Fernandez, E., DI MARINO, D., Buzzi, A., et al. (2013). CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic Spine formation. NEURON, 79(6), 1169-1182 [10.1016/j.neuron.2013.06.039].

CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic Spine formation

DI MARINO, DANIELE;BAGNI, CLAUDIA
2013

Abstract

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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/13
English
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
Derubeis, S., Pasciuto, E., Li, K., Fernandez, E., DI MARINO, D., Buzzi, A., et al. (2013). CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic Spine formation. NEURON, 79(6), 1169-1182 [10.1016/j.neuron.2013.06.039].
Derubeis, S; Pasciuto, E; Li, K; Fernandez, E; DI MARINO, D; Buzzi, A; Ostroff, L; Klann, E; Zwartkruis, F; Komiyama, N; Grant, S; Poujol, C; Choquet, D; Achsel, T; Posthuma, D; Smit, A; Bagni, C
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/136339
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