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
Neuron. 2013-09-01; 79(6): 1169-1182
DOI: 10.1016/j.neuron.2013.06.039

PubMed
Read on PubMed



1. Neuron. 2013 Sep 18;79(6):1169-82. doi: 10.1016/j.neuron.2013.06.039.

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

De Rubeis S(1), Pasciuto E, Li KW, Fernández E, Di Marino D, Buzzi A, Ostroff LE,
Klann E, Zwartkruis FJ, Komiyama NH, Grant SG, Poujol C, Choquet D, Achsel T,
Posthuma D, Smit AB, Bagni C.

Author information:
(1)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.

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.

Copyright © 2013 Elsevier Inc. All rights reserved.

DOI: 10.1016/j.neuron.2013.06.039
PMCID: PMC3781321
PMID: 24050404 [Indexed for MEDLINE]

Know more about