miR-132 Regulates Dendritic Spine Structure by Direct Targeting of Matrix Metalloproteinase 9 mRNA

• Published in: Molecular neurobiology Vol. 53; no. 7; pp. 4701 - 4712
• Main Authors: Jasińska, Magdalena, Miłek, Jacek, Cymerman, Iwona A., Łęski, Szymon, Kaczmarek, Leszek, Dziembowska, Magdalena
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2016; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Brain; Cell Biology; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - metabolism; Cerebral Cortex - secretion; Dendritic Spines - metabolism; HEK293 Cells; Hippocampus - cytology; Hippocampus - metabolism; Hippocampus - secretion; Humans; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinase 9 - secretion; Mice; Mice, Knockout; MicroRNAs - biosynthesis; Neurobiology; Neurology; Neuronal Plasticity - physiology; Neurons; Neurosciences; Proteins; Rats; RNA, Messenger - metabolism; Spine; Synaptosomes - metabolism; Synaptosomes - secretion; miR-132; Matrix metalloproteinase 9 (MMP-9); Structural plasticity of dendritic spines
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-015-9383-z

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.