CYFIP/Sra-1 controls neuronal connectivity in Drosophila and links the Rac1 GTPase pathway to the fragile X protein

Neuron. 2003 Jun 19;38(6):887-98. doi: 10.1016/s0896-6273(03)00354-4.

Abstract

Neuronal plasticity requires actin cytoskeleton remodeling and local protein translation in response to extracellular signals. Rho GTPase pathways control actin reorganization, while the fragile X mental retardation protein (FMRP) regulates the synthesis of specific proteins. Mutations affecting either pathway produce neuronal connectivity defects in model organisms and mental retardation in humans. We show that CYFIP, the fly ortholog of vertebrate FMRP interactors CYFIP1 and CYFIP2, is specifically expressed in the nervous system. CYFIP mutations affect axons and synapses, much like mutations in dFMR1 (the Drosophila FMR1 ortholog) and in Rho GTPase dRac1. CYFIP interacts biochemically and genetically with dFMR1 and dRac1. Finally, CYFIP acts as a dRac1 effector that antagonizes FMR1 function, providing a bridge between signal-dependent cytoskeleton remodeling and translation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Axons / physiology
  • Axons / ultrastructure
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cloning, Molecular
  • Cytoskeleton / physiology
  • Cytoskeleton / ultrastructure
  • Drosophila / growth & development
  • Drosophila / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology
  • Eye / anatomy & histology
  • Eye / metabolism
  • Fragile X Mental Retardation Protein
  • GTP Phosphohydrolases / metabolism
  • Gene Deletion
  • Gene Expression
  • Mutagenesis
  • Mutation
  • Neuromuscular Junction / ultrastructure
  • Neuronal Plasticity
  • Neurons / physiology*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / physiology*
  • Signal Transduction
  • Synapses / ultrastructure
  • rac GTP-Binding Proteins / genetics
  • rac GTP-Binding Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Drosophila Proteins
  • FMR1 protein, Drosophila
  • RNA-Binding Proteins
  • Rac1 protein, Drosophila
  • Sra-1 protein, Drosophila
  • Fragile X Mental Retardation Protein
  • GTP Phosphohydrolases
  • rac GTP-Binding Proteins