The fragile X mental retardation protein-RNP granules show an mGluR-dependent localization in the post-synaptic spines

Mol Cell Neurosci. 2007 Mar;34(3):343-54. doi: 10.1016/j.mcn.2006.11.015. Epub 2007 Jan 23.

Abstract

The localization of RNA/mRNA in dendrites plays a role in both local and temporal regulation of protein synthesis, which is required for certain forms of synaptic plasticity. A key molecule in these processes is the fragile X mental retardation protein (FMRP). Using in situ hybridization coupled to immunofluorescence confocal microscopy, we find that the FMRP-RNP particle contains alphaCaMKII and BC1 RNAs as well as Staufen and CPEB proteins. Furthermore, following mGluR activation, the FMRP-mRNP complex moves into spines as shown by co-localization with the PSD-95 and Shank proteins. This study shows, for the first time, that the translationally inactive FMRP-mRNP complex relocates into neuronal spines after stimulation and that de novo protein synthesis mainly contributes to the pool of FMRP at synapses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cricetinae
  • Dendritic Spines / drug effects
  • Dendritic Spines / metabolism*
  • Disks Large Homolog 4 Protein
  • Embryo, Mammalian
  • Fluorescent Antibody Technique / methods
  • Fragile X Mental Retardation Protein / metabolism*
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / physiology
  • Guanylate Kinases
  • In Situ Hybridization
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / metabolism
  • Methoxyhydroxyphenylglycol / analogs & derivatives
  • Methoxyhydroxyphenylglycol / pharmacology
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology*
  • RNA-Binding Proteins / metabolism
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / physiology*
  • Time Factors
  • Transfection
  • tau Proteins / metabolism

Substances

  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Mtap2 protein, mouse
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Receptors, Metabotropic Glutamate
  • Stau1 protein, mouse
  • tau Proteins
  • Fragile X Mental Retardation Protein
  • Methoxyhydroxyphenylglycol
  • Guanylate Kinases
  • 3,4-dihydroxyphenylglycol