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

Research output: Contribution to journalArticle

  • 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

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http://www.cell.com/neuron/retrieve/pii/S0896627313005552
Original languageEnglish
Pages (from-to)1169-82
Number of pages14
JournalNeuron
Volume79
Issue number6
DOIs
Publication statusPublished - 18 Sep 2013

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.

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