Localization of FMRP-associated mRNA granules and requirement of microtubules for activity-dependent trafficking in hippocampal neurons

Genes Brain Behav. 2005 Aug;4(6):350-9. doi: 10.1111/j.1601-183X.2005.00128.x.


Fragile X syndrome is caused by the absence of the fragile X mental-retardation protein (FMRP), an mRNA-binding protein, which may play important roles in the regulation of dendritic mRNA localization and/or synaptic protein synthesis. We have recently applied high-resolution fluorescence imaging methods to document the presence, motility and activity-dependent regulation of FMRP granule trafficking in dendrites and spines of cultured hippocampal neurons. In this study, we show that FMRP granules distribute to F-actin-rich compartments, including filopodia, spines and growth cones during the staged development of hippocampal neurons in culture. Fragile X mental-retardation protein granules were shown to colocalize with ribosomes, ribosomal RNA and MAP1B mRNA, a known FMRP target, which encodes a protein important for microtubule and actin stabilization. The levels of FMRP within dendrites were reduced by disruption of microtubule dynamics, but not by disruption of F-actin. Direct measurements of FMRP transport kinetics using fluorescence recovery after photobleaching in living neurons showed that microtubules were required to induce the mGluR-dependent translocation into dendrites. This study provides further characterization of the composition and regulated trafficking of FMRP granules in dendrites of hippocampal neurons.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Actins / ultrastructure
  • Animals
  • Cells, Cultured
  • Cytoplasmic Granules / metabolism*
  • Cytoplasmic Granules / ultrastructure
  • Dendritic Spines / metabolism
  • Dendritic Spines / ultrastructure
  • Fluorescence Recovery After Photobleaching
  • Fragile X Mental Retardation Protein
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / metabolism
  • Fragile X Syndrome / physiopathology
  • Growth Cones / metabolism
  • Growth Cones / ultrastructure
  • Hippocampus / metabolism*
  • Hippocampus / ultrastructure
  • Immunohistochemistry
  • Microscopy, Electron, Transmission
  • Microtubule-Associated Proteins / genetics
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Protein Transport / physiology
  • Pseudopodia / metabolism
  • Pseudopodia / ultrastructure
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Rats
  • Ribosomes / genetics
  • Ribosomes / metabolism


  • Actins
  • Fmr1 protein, rat
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • microtubule-associated protein 1B
  • Fragile X Mental Retardation Protein