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

Silvia DeRubeis, Emanuela Pasciuto, KaWan Li, Esperanza Fernández, Daniele DiMarino, Andrea Buzzi, LinnaeaE Ostroff, Eric Klann, Fried J T Zwartkruis, NoboruH Komiyama, Seth G N Grant, Christel Poujol, Daniel Choquet, Tilmann Achsel, Danielle Posthuma, AugustB Smit, Claudia Bagni

Research output: Contribution to journalArticle

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

Original languageEnglish (US)
Pages (from-to)1169-1182
Number of pages14
JournalNeuron
Volume79
Issue number6
DOIs
StatePublished - Sep 18 2013

Fingerprint

Dendritic Spines
Protein Biosynthesis
Cytoskeleton
Actins
Spine
Brain-Derived Neurotrophic Factor
Brain Diseases
Autistic Disorder
Nervous System Diseases
Intellectual Disability
Polymerization
Schizophrenia
Neurons
Genes
Proteins

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

DeRubeis, S., Pasciuto, E., Li, K., Fernández, E., DiMarino, D., Buzzi, A., ... Bagni, C. (2013). CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic Spine formation. Neuron, 79(6), 1169-1182. https://doi.org/10.1016/j.neuron.2013.06.039

CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic Spine formation. / DeRubeis, Silvia; Pasciuto, Emanuela; Li, KaWan; Fernández, Esperanza; DiMarino, Daniele; Buzzi, Andrea; Ostroff, LinnaeaE; Klann, Eric; Zwartkruis, Fried J T; Komiyama, NoboruH; Grant, Seth G N; Poujol, Christel; Choquet, Daniel; Achsel, Tilmann; Posthuma, Danielle; Smit, AugustB; Bagni, Claudia.

In: Neuron, Vol. 79, No. 6, 18.09.2013, p. 1169-1182.

Research output: Contribution to journalArticle

DeRubeis, S, Pasciuto, E, Li, K, Fernández, E, DiMarino, D, Buzzi, A, Ostroff, L, Klann, E, Zwartkruis, FJT, Komiyama, N, Grant, SGN, Poujol, C, Choquet, D, Achsel, T, Posthuma, D, Smit, A & Bagni, C 2013, 'CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic Spine formation', Neuron, vol. 79, no. 6, pp. 1169-1182. https://doi.org/10.1016/j.neuron.2013.06.039
DeRubeis S, Pasciuto E, Li K, Fernández E, DiMarino D, Buzzi A et al. CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic Spine formation. Neuron. 2013 Sep 18;79(6):1169-1182. https://doi.org/10.1016/j.neuron.2013.06.039
DeRubeis, Silvia ; Pasciuto, Emanuela ; Li, KaWan ; Fernández, Esperanza ; DiMarino, Daniele ; Buzzi, Andrea ; Ostroff, LinnaeaE ; Klann, Eric ; Zwartkruis, Fried J T ; Komiyama, NoboruH ; Grant, Seth G N ; Poujol, Christel ; Choquet, Daniel ; Achsel, Tilmann ; Posthuma, Danielle ; Smit, AugustB ; Bagni, Claudia. / CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic Spine formation. In: Neuron. 2013 ; Vol. 79, No. 6. pp. 1169-1182.
@article{ee3698c869a64d6b9d6a024ff199bfa0,
title = "CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic Spine formation",
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",
author = "Silvia DeRubeis and Emanuela Pasciuto and KaWan Li and Esperanza Fern{\'a}ndez and Daniele DiMarino and Andrea Buzzi and LinnaeaE Ostroff and Eric Klann and Zwartkruis, {Fried J T} and NoboruH Komiyama and Grant, {Seth G N} and Christel Poujol and Daniel Choquet and Tilmann Achsel and Danielle Posthuma and AugustB Smit and Claudia Bagni",
year = "2013",
month = "9",
day = "18",
doi = "10.1016/j.neuron.2013.06.039",
language = "English (US)",
volume = "79",
pages = "1169--1182",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "6",

}

TY - JOUR

T1 - CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic Spine formation

AU - DeRubeis, Silvia

AU - Pasciuto, Emanuela

AU - Li, KaWan

AU - Fernández, Esperanza

AU - DiMarino, Daniele

AU - Buzzi, Andrea

AU - Ostroff, LinnaeaE

AU - Klann, Eric

AU - Zwartkruis, Fried J T

AU - Komiyama, NoboruH

AU - Grant, Seth G N

AU - Poujol, Christel

AU - Choquet, Daniel

AU - Achsel, Tilmann

AU - Posthuma, Danielle

AU - Smit, AugustB

AU - Bagni, Claudia

PY - 2013/9/18

Y1 - 2013/9/18

N2 - 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

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

UR - http://www.scopus.com/inward/record.url?scp=84884215045&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884215045&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2013.06.039

DO - 10.1016/j.neuron.2013.06.039

M3 - Article

C2 - 24050404

AN - SCOPUS:84884215045

VL - 79

SP - 1169

EP - 1182

JO - Neuron

JF - Neuron

SN - 0896-6273

IS - 6

ER -