Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, DEPENDENT TRANSLATION, LOCALIZATION, MINOCYCLINE, GRANULES, ACTIVATION, MATURATION, RECEPTOR, NEURONS, MATRIX, MODEL, Animals, Dendrites, Female, Fragile X Mental Retardation Protein, Hippocampus, Matrix Metalloproteinase 9, Mice, Mice, Knockout, RNA, Messenger, Rats, Synapses, 11 Medical and Health Sciences, 17 Psychology and Cognitive Sciences, Neurology & Neurosurgery, 3209 Neurosciences

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.