The Fragile X mental retardation protein regulates matrix metalloproteinase 9 mRNA at synapses

J Neurosci. 2013 Nov 13;33(46):18234-41. doi: 10.1523/JNEUROSCI.2207-13.2013.


Activity-dependent protein synthesis at synapses is dysregulated in the Fragile X syndrome (FXS). This process contributes to dendritic spine dysmorphogenesis and synaptic dysfunction in FXS. Matrix Metalloproteinase 9 (MMP-9) is an enzyme involved in activity-dependent reorganization of dendritic spine architecture and was shown to regulate spine morphology in a mouse model of FXS, the Fmr1 knock-out mice. Here we show that MMP-9 mRNA is part of the FMRP complex and colocalizes in dendrites. In the absence of FMRP MMP-9 mRNA translation is increased at synapses, suggesting that this mechanism contributes to the increased metalloproteinase level at synapses of Fmr1 knock-out mice. We propose that such a local effect can contribute to the aberrant dendritic spine morphology observed in the Fmr1 knock-out mice and in patients with FXS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendrites / enzymology
  • Dendrites / genetics
  • Female
  • Fragile X Mental Retardation Protein / physiology*
  • Hippocampus / enzymology
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Matrix Metalloproteinase 9 / genetics
  • Mice
  • Mice, Knockout
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • Rats
  • Synapses / enzymology*
  • Synapses / genetics


  • Fmr1 protein, mouse
  • RNA, Messenger
  • Fragile X Mental Retardation Protein
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse