The Fragile X mental retardation protein regulates matrix metalloproteinase 9 mRNA at synapses.
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.
Laboratory of Neurobiology, The Nencki Institute, 02-093 Warsaw, Poland, Institute of Biochemistry and Biophysics, 02-106 Warsaw, Poland, Laboratory of Molecular and Cellular Neurobiology, The International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland, Department of Biomedicine and Prevention, University "Tor Vergata," 00133 Rome, Italy, VIB Center for the Biology of Disease, 3000 Leuven, Belgium, and Center for Human Genetics, KU Leuven, 3000 Leuven, Belgium.
Aleksandra
A
Janusz
Jacek
J
Milek
Malgorzata
M
Perycz
Laura
L
Pacini
Claudia
C
Bagni
Leszek
L
Kaczmarek
Magdalena
M
Dziembowska
D000818:Animals; D003712:Dendrites / Q000201:enzymology / Q000235:genetics; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000502:physiology*; D006624:Hippocampus / Q000201:enzymology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D013569:Synapses / Q000201:enzymology* / Q000235:genetics
D051860:Fragile X Messenger Ribonucleoprotein 1; D020780:Matrix Metalloproteinase 9; D012333:RNA, Messenger; C497684:Fmr1 protein, mouse; C501830:Mmp9 protein, mouse