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

Silvia De Rubeis; Emanuela Pasciuto; Ka Wan Li; Esperanza Fernández; Daniele Di Marino; Andrea Buzzi; Linnaea E Ostroff; Eric Klann; Fried J T Zwartkruis; Noboru H Komiyama; Seth G N Grant; Christel Poujol; Daniel Choquet; Tilmann Achsel; Danielle Posthuma; August B Smit; Claudia Bagni

doi:10.1016/j.neuron.2013.06.039

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

Silvia De Rubeis, Emanuela Pasciuto, Ka Wan Li, Esperanza Fernández, Daniele Di Marino, Andrea Buzzi, Linnaea E Ostroff, Eric Klann, Fried J T Zwartkruis, Noboru H Komiyama, Seth G N Grant, Christel Poujol, Daniel Choquet, Tilmann Achsel, Danielle Posthuma, August B Smit, Claudia Bagni

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	1169-82
Number of pages	14
Journal	Neuron
Volume	79
Issue number	6
DOIs	https://doi.org/10.1016/j.neuron.2013.06.039
Publication status	Published - 18 Sept 2013

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CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine FormationFinal published version, 2.49 MB

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De Rubeis, S., Pasciuto, E., Li, K. W., Fernández, E., Di Marino, D., Buzzi, A., Ostroff, L. E., Klann, E., Zwartkruis, F. J. T., Komiyama, N. H., Grant, S. G. N., Poujol, C., Choquet, D., Achsel, T., Posthuma, D., Smit, A. B., & Bagni, C. (2013). CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation. Neuron, 79(6), 1169-82. https://doi.org/10.1016/j.neuron.2013.06.039

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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 = "{De Rubeis}, Silvia and Emanuela Pasciuto and Li, {Ka Wan} and Esperanza Fern{\'a}ndez and {Di Marino}, Daniele and Andrea Buzzi and Ostroff, {Linnaea E} and Eric Klann and Zwartkruis, {Fried J T} and Komiyama, {Noboru H} and Grant, {Seth G N} and Christel Poujol and Daniel Choquet and Tilmann Achsel and Danielle Posthuma and Smit, {August B} and Claudia Bagni",

note = "Wellcome Trust funding for S.G.N.G",

year = "2013",

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doi = "10.1016/j.neuron.2013.06.039",

language = "English",

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De Rubeis, S, Pasciuto, E, Li, KW, Fernández, E, Di Marino, D, Buzzi, A, Ostroff, LE, Klann, E, Zwartkruis, FJT, Komiyama, NH , Grant, SGN, Poujol, C, Choquet, D, Achsel, T, Posthuma, D, Smit, AB & Bagni, C 2013, 'CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation', Neuron, vol. 79, no. 6, pp. 1169-82. https://doi.org/10.1016/j.neuron.2013.06.039

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T1 - CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation

AU - De Rubeis, Silvia

AU - Pasciuto, Emanuela

AU - Li, Ka Wan

AU - Fernández, Esperanza

AU - Di Marino, Daniele

AU - Buzzi, Andrea

AU - Ostroff, Linnaea E

AU - Klann, Eric

AU - Zwartkruis, Fried J T

AU - Komiyama, Noboru H

AU - Grant, Seth G N

AU - Poujol, Christel

AU - Choquet, Daniel

AU - Achsel, Tilmann

AU - Posthuma, Danielle

AU - Smit, August B

AU - Bagni, Claudia

N1 - Wellcome Trust funding for S.G.N.G

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.

U2 - 10.1016/j.neuron.2013.06.039

DO - 10.1016/j.neuron.2013.06.039

M3 - Article

C2 - 24050404

SN - 0896-6273

VL - 79

SP - 1169

EP - 1182

JO - Neuron

JF - Neuron

IS - 6

ER -

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

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