TY - JOUR
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 -