Activity-Dependent Local Translation of Matrix Metalloproteinase-9
| Autor: | Jacek Milek, Ewelina Romanowska, Magdalena Dziembowska, Aleksandra Janusz, Adrian Tiron, Emilia Rejmak, Leszek Kaczmarek, Clive R. Bramham, Tomasz Gorkiewicz |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Perforant Pathway Primary Cell Culture Biology Hippocampus Rats Sprague-Dawley Polysome Protein biosynthesis Animals General Neuroscience Dentate gyrus Glutamate receptor Long-term potentiation Articles Dendrites Rats Cell biology Transport protein Enzyme Activation Protein Transport Matrix Metalloproteinase 9 Biochemistry Dendritic transport Protein Biosynthesis Synaptic plasticity Synaptosomes |
| Zdroj: | The Journal of Neuroscience. 32:14538-14547 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.6028-11.2012 |
| Popis: | Local, synaptic synthesis of new proteins in response to neuronal stimulation plays a key role in the regulation of synaptic morphogenesis. Recent studies indicate that matrix metalloproteinase-9 (MMP-9), an endopeptidase that regulates the pericellular environment through cleavage of its protein components, plays a critical role in regulation of spine morphology and synaptic plasticity. Here, we sought to determine whether MMP-9 mRNA is transported to dendrites for local translation and protein release. First, dendritic transport of MMP-9 mRNA was seen in primary hippocampal neuronal cultures treated with glutamate and in dentate gyrus granule cells in adult anesthetized rats after induction of long-term potentiation. Second, rapid, activity-dependent polyadenylation of MMP-9 mRNA; association of the mRNA with actively translating polysomes; andde novoMMP-9 protein synthesis were obtained in synaptoneurosomes isolated from rat hippocampus. Third, glutamate stimulation of cultured hippocampal neurons evoked a rapid (in minutes) increase in MMP-9 activity, as measured by cleavage of its native substrate, β-dystroglycan. This activity was reduced by the polyadenylation inhibitor, thus linking MMP-9 translation with protein function. In aggregate, our findings show that MMP-9 mRNA is transported to dendrites and locally translated and that the protein is released in an activity-dependent manner. Acting in concert with other dendritically synthesized proteins, locally secreted MMP-9 may contribute to the structural and functional plasticity of the activated synapses. |
| Databáze: | OpenAIRE |
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