title: miR-132 Regulates Dendritic Spine Structure by Direct Targeting of Matrix Metalloproteinase 9 mRNA.
abstract: Mir-132 is a neuronal activity-regulated microRNA that controls the morphology of dendritic spines and neuronal transmission. Similar activities have recently been attributed to matrix metalloproteinase-9 (MMP-9), an extrasynaptic protease. In the present study, we provide evidence that miR-132 directly regulates MMP-9 mRNA in neurons to modulate synaptic plasticity. With the use of luciferase reporter system, we show that miR-132 binds to the 3'UTR of MMP-9 mRNA to regulate its expression in neurons. The overexpression of miR-132 in neurons reduces the level of endogenous MMP-9 protein secretion. In synaptoneurosomes, metabotropic glutamate receptor (mGluR)-induced signaling stimulates the dissociation of miR-132 from polyribosomal fractions and shifts it towards the messenger ribonucleoprotein (mRNP)-containing fraction. Furthermore, we demonstrate that the overexpression of miR-132 in the cultured hippocampal neurons from Fmr1 KO mice that have increased synaptic MMP-9 level provokes enlargement of the dendritic spine heads, a process previously implicated in enhanced synaptic plasticity. We propose that activity-dependent miR-132 regulates structural plasticity of dendritic spines through matrix metalloproteinase 9.
authors: Laboratory of Neurobiology, The Nencki Institute, Pasteura 3, 02-093, Warsaw, Poland.|Laboratory of Molecular Basis of Synaptic Plasticity, Center of New Technologies, University of Warsaw, Warsaw, Poland.|School of Molecular Medicine, Żwirki i Wigury 61, 02-091, Warsaw, Poland.
authors: Magdalena
authors: M
authors: Jasińska
authors: Laboratory of Neurobiology, The Nencki Institute, Pasteura 3, 02-093, Warsaw, Poland.|Laboratory of Molecular Basis of Synaptic Plasticity, Center of New Technologies, University of Warsaw, Warsaw, Poland.|Institute of Biochemistry and Biophysics, 02-106, Warsaw, Poland.
authors: Jacek
authors: J
authors: Miłek
authors: Laboratory of Molecular and Cellular Neurobiology, The International Institute of Molecular and Cell Biology, Warsaw, Poland.
authors: Iwona A
authors: IA
authors: Cymerman
authors: Laboratory of Neuroinformatics, The Nencki Institute, Pasteura 3, 02-093, Warsaw, Poland.
authors: Szymon
authors: S
authors: Łęski
authors: Laboratory of Neurobiology, The Nencki Institute, Pasteura 3, 02-093, Warsaw, Poland. l.kaczmarek@nencki.gov.pl.
authors: Leszek
authors: L
authors: Kaczmarek
authors: Laboratory of Neurobiology, The Nencki Institute, Pasteura 3, 02-093, Warsaw, Poland. m.dziembowska@nencki.gov.pl.|Laboratory of Molecular Basis of Synaptic Plasticity, Center of New Technologies, University of Warsaw, Warsaw, Poland. m.dziembowska@nencki.gov.pl.
authors: Magdalena
authors: M
authors: Dziembowska
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism*; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000096:biosynthesis*; D009473:Neuronal Plasticity / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D013574:Synaptosomes / Q000378:metabolism
chemical_list: C546976:MIRN132 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: Matrix metalloproteinase 9 (MMP-9); Structural plasticity of dendritic spines; miR-132