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Title: CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation
Authors: De Rubeis, Silvia ×
Pasciuto, Emanuela
Li, Ka Wan
Fernández, Esperanza
Di Marino, Daniele
Buzzi, Andrea
Ostroff, Linnaea E
Klann, Eric
Zwartkruis, Fried J T
Komiyama, Noboru H
Grant, Seth G N
Poujol, Christel
Choquet, Daniel
Achsel, Tilmann
Posthuma, Danielle
Smit, August B
Bagni, Claudia #
Issue Date: Sep-2013
Publisher: Cell Press
Series Title: Neuron vol:79 issue:6 pages:1169-82
Article number: 10.1016/j.neuron.2013.06.039
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.
URI: 
ISSN: 0896-6273
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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