Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function

Cell. 2001 Nov 30;107(5):591-603. doi: 10.1016/s0092-8674(01)00589-x.


Fragile X mental retardation gene (FMR1) encodes an RNA binding protein that acts as a negative translational regulator. We have developed a Drosophila fragile X syndrome model using loss-of-function mutants and overexpression of the FMR1 homolog (dfxr). dfxr nulls display enlarged synaptic terminals, whereas neuronal overexpression results in fewer and larger synaptic boutons. Synaptic structural defects are accompanied by altered neurotransmission, with synapse type-specific regulation in central and peripheral synapses. These phenotypes mimic those observed in mutants of microtubule-associated Futsch. Immunoprecipitation of dFXR shows association with futsch mRNA, and Western analyses demonstrate that dFXR inversely regulates Futsch expression. dfxr futsch double mutants restore normal synaptic structure and function. We propose that dFXR acts as a translational repressor of Futsch to regulate microtubule-dependent synaptic growth and function.

Publication types

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

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / physiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology*
  • Electroretinography
  • Evoked Potentials / physiology
  • Flight, Animal / physiology
  • Fragile X Mental Retardation Protein
  • Gene Expression Regulation
  • Genes, Insect
  • Humans
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Molecular Sequence Data
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuromuscular Junction / cytology
  • Neuromuscular Junction / physiology*
  • Neurons / cytology
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Photoreceptor Cells, Invertebrate / growth & development
  • Photoreceptor Cells, Invertebrate / physiology
  • RNA-Binding Proteins*
  • Synapses / physiology*


  • Drosophila Proteins
  • FMR1 protein, human
  • Microtubule-Associated Proteins
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • futsch protein, Drosophila
  • microtubule-associated protein 1B
  • Fragile X Mental Retardation Protein

Associated data

  • GENBANK/AF205596
  • GENBANK/AF205597
  • GENBANK/AJ271221