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Articles, Cellular/Molecular

The Fragile X Mental Retardation Protein Regulates Matrix Metalloproteinase 9 mRNA at Synapses

Aleksandra Janusz, Jacek Miłek, Małgorzata Perycz, Laura Pacini, Claudia Bagni, Leszek Kaczmarek and Magdalena Dziembowska
Journal of Neuroscience 13 November 2013, 33 (46) 18234-18241; DOI: https://doi.org/10.1523/JNEUROSCI.2207-13.2013
Aleksandra Janusz
1Laboratory of Neurobiology, The Nencki Institute, 02-093 Warsaw, Poland,
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Jacek Miłek
1Laboratory of Neurobiology, The Nencki Institute, 02-093 Warsaw, Poland,
2Institute of Biochemistry and Biophysics, 02-106 Warsaw, Poland,
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Małgorzata Perycz
3Laboratory of Molecular and Cellular Neurobiology, The International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland,
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Laura Pacini
4Department of Biomedicine and Prevention, University “Tor Vergata,” 00133 Rome, Italy,
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Claudia Bagni
4Department of Biomedicine and Prevention, University “Tor Vergata,” 00133 Rome, Italy,
5VIB Center for the Biology of Disease, 3000 Leuven, Belgium, and
6Center for Human Genetics, KU Leuven, 3000 Leuven, Belgium
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Leszek Kaczmarek
1Laboratory of Neurobiology, The Nencki Institute, 02-093 Warsaw, Poland,
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Magdalena Dziembowska
1Laboratory of Neurobiology, The Nencki Institute, 02-093 Warsaw, Poland,
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Abstract

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.

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The Journal of Neuroscience: 33 (46)
Journal of Neuroscience
Vol. 33, Issue 46
13 Nov 2013
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The Fragile X Mental Retardation Protein Regulates Matrix Metalloproteinase 9 mRNA at Synapses
Aleksandra Janusz, Jacek Miłek, Małgorzata Perycz, Laura Pacini, Claudia Bagni, Leszek Kaczmarek, Magdalena Dziembowska
Journal of Neuroscience 13 November 2013, 33 (46) 18234-18241; DOI: 10.1523/JNEUROSCI.2207-13.2013

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The Fragile X Mental Retardation Protein Regulates Matrix Metalloproteinase 9 mRNA at Synapses
Aleksandra Janusz, Jacek Miłek, Małgorzata Perycz, Laura Pacini, Claudia Bagni, Leszek Kaczmarek, Magdalena Dziembowska
Journal of Neuroscience 13 November 2013, 33 (46) 18234-18241; DOI: 10.1523/JNEUROSCI.2207-13.2013
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