title: Drosophila fragile X-related gene regulates the MAP1B homolog Futsch to control synaptic structure and function.
abstract: 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.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Zhang
authors.forename: A M
authors.initials: AM
authors.lastname: Bailey
authors.forename: H J
authors.initials: HJ
authors.lastname: Matthies
authors.forename: R B
authors.initials: RB
authors.lastname: Renden
authors.forename: M A
authors.initials: MA
authors.lastname: Smith
authors.forename: S D
authors.initials: SD
authors.lastname: Speese
authors.forename: G M
authors.initials: GM
authors.lastname: Rubin
authors.forename: K
authors.initials: K
authors.lastname: Broadie
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D004596:Electroretinography; D005071:Evoked Potentials / Q000502:physiology; D005426:Flight, Animal / Q000502:physiology; D051860:Fragile X Messenger Ribonucleoprotein 1; D005786:Gene Expression Regulation; D017344:Genes, Insect; D006801:Humans; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology; D018408:Patch-Clamp Techniques; D017956:Photoreceptor Cells, Invertebrate / Q000254:growth & development / Q000502:physiology; D016601:RNA-Binding Proteins; D013569:Synapses / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D008869:Microtubule-Associated Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human; C409635:futsch protein, Drosophila; C085284:microtubule-associated protein 1B