EN
Recent studies have implicated MMP-9 in schizophrenia, in particular, Domenici et al reported highly elevated plasma levels of MMP-9 in schizophrenic patients and Rybakowski et al. demonstrated an association of MMP-9 5’UTR polymorphism -1562C/T with schizophrenia. Furthermore, Dziembowska et al. have shown that MMP-9 is locally translated in neurons in response to synaptic stimulation. Since 3’UTR plays essential role in mRNA transport to the dendrites and in its local translation, MMP-9 3’UTR polymorphisms may affect synaptic availability of the enzyme. In order to verify if SNPs affect local translation of MMP-9 or its mRNA transport we have made two types of vectors with human MMP-9 containing two 3’UTR variants as well as the inactive form of MMP-9 under human synapsin I promoter. The gene constructs enable MMP-9 protein visualization by its fusion to Venus fluorescent protein and additionally contain myristoylation sequence, which is responsible for the cell membrane docking. In result, locally translated MMP-9 at the synapse could be observed. Currently, we investigate if the polymorphism influences efficiency of MMP-9 mRNA transport and local translation under basal conditions or after stimulation. To enable MMP-9 mRNA tracking in the dendrites we will use MS2 system on living neurons under basal conditions and after stimulation of the two studied 3’UTR variants.