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Signaling Through Proteolysis

We have recently reported that matrix metalloproteinase-9 (MMP-9) is upregulated in the dentate gyrus neurons of the hippocampus in response to kainate-evoked seizures. This upregulation was observed at the level of mRNA abundance and its apparent translocation toward the activated dendrites. Furthermore, enzymatic activity of the MMP-9 was markedly increased throughout the dentate gyrus and dendrites of the granule neurons. We have also proposed that MMP-9 may be directly involved in breaking down beta-dystroglycan at the synapse, and thus may play a role in spreading a retrograde synaptic signals. Recently, we have found further evidence for synaptic localization and function of the MMP-9. In aggregate, an analysis of MMP-9 expression pattern in the brain, along with identification of dystroglycan as its substrate suggests that MMP-9 may play an important role in the neuronal physiology, especially in neuronal plasticity, including its direct participation in remodeling of synaptic connections, a mechanism pivotal for learning and memory.