TY - JOUR
T1 - CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic Spine formation
AU - DeRubeis, Silvia
AU - Pasciuto, Emanuela
AU - Li, Ka Wan
AU - Fernández, Esperanza
AU - DiMarino, 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 - Funding Information:
We thank Ilaria Napoli and Tiziana Girardi for preliminary data. We are grateful to Evita Mohr and Joachim Kremerskothen for the PABP1 and SYNCRIP antibodies. We are grateful to Elien Theuns, Jonathan Royaert, Karin Jonkers, Ingeborg Beheydt, and Roel van der Schors for technical help and to Bing Yan for viral production. We are thankful to Paul Woolley, Carolina Barillas, and Giovanni Chillemi for comments on the manuscript and to Sebastian Munck, coordinator of LiMoNe, for his advice. S.D.R. was supported by the Associazione Italiana Sindrome X Fragile and by a Fonds Wetenschappelijk Onderzoek (FWO) grant to C.B. (FWO G.0705.11); E.P. was supported by an FWO (aspirant fellowship); D.D.M was supported by an FWO grant to C.B. (FWO G.0705.11); E.F. was supported by an Intra-European Marie Curie Fellowship FP7. We are indebted to the Schizophrenia subgroup of the Psychiatric Genetics Consortium for providing access to the results of their meta-analysis. This work was supported by grants from the following agencies: Queen Elisabeth Foundation (Belgium), CARIPLO, FWO (FWO G.0705.11), VIB, and Telethon (GGP10150) to C.B.; HEALTH-2009-2.1.2-1 EU-FP7 “SynSys” to A.B.S., S.G.N.G., and C.B.; FP7 GENCODYS and EU-FP7 “EUROSPIN” to A.B.S. and S.G.N.G.; Wellcome Trust to S.G.N.G.; and the Center for Medical Systems Biology (CMSB) to A.B.S. Nikon microscope used in this study was acquired through a Hercules Type 1 AKUL/09/037 to Wim Annaert. We are very grateful to Eef Lemmens for administrative support.
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
U2 - 10.1016/j.neuron.2013.06.039
DO - 10.1016/j.neuron.2013.06.039
M3 - Article
C2 - 24050404
AN - SCOPUS:84884215045
SN - 0896-6273
VL - 79
SP - 1169
EP - 1182
JO - Neuron
JF - Neuron
IS - 6
ER -