Molecules in focusMMP9: A novel function in synaptic plasticity
Highlights
► MMP-9 mRNA is locally translated in neurons and released in response to enhanced synaptic activity. ► MMP-9 is present at the dendritic spines bearing asymmetric synapses. ► MMP-9 influences dendritic spine morphology and plays a key role in synaptic plasticity associated with learning and memory.
Introduction
The matrix metalloproteinases (MMPs) are a family of zinc-dependent enzymes which operate extracellularly and are able to degrade components of the extracellular matrix ECM (Woessner, 1991).
Section snippets
Structure
The primary structure of MMP-9 (gelatinase B) (EC 3.4.24.25) starting from N-terminus is composed of the following domains: a signal peptide, a propeptide, a catalytic domain that may bind a zinc ion, a three tandem repeats of fibronectin type II inserts within the catalytic domain, a proline-rich and heavily O-glycosylated linker, and a hemopexin-like domain (Stute et al., 2003) (Fig. 1). The propeptide domain contains conserved PRCGVPDV motive that binds to the zinc ion of the catalytic
Expression and activation in neurons
MMP-9 is an important enzyme involved in matrix remodeling during the normal processes of embryogenesis, tissue remodeling and development. In addition to its role in maintaining tissue homeostasis MMP-9 was shown to be activated in such pathologies as cancer (it modulates tumor micro-environment and enhances metastasis) or in acute and chronic neurological conditions e.g. stroke or multiple sclerosis (Kessenbrock et al., 2010; Yong et al., 2005). Recently, MMP-9 has also emerged as a novel
Role in synaptic plasticity
The synaptic plasticity may be defined as a re-organization of the synaptic connections that comprises both, alterations at the morphological level and changes at the functional level. Enhanced neuronal activity and some aspects of plasticity are mimicked by experimental paradigms such as long-term potentiation (LTP).
Recent studies indicate that spine structure can be regulated by extracellular matrix (ECM). Notably, an involvement of MMP-9 in modulation of morphology of the dendritic spines
Conclusions
Matrix metaloproteinase-9 undergoes very complex regulation; it is secreted and activated in the extracellular space in response to enhanced neuronal activity. This enzyme can cleave and release signaling molecules from CAMs, which may affect morphology of existing dendritic spines. This effect is most probably mediated by integrin dependent signaling. Pivotal role of MMP-9 in the synaptic plasticity at the level of gene expression, changes in dendritic spine morphology and synaptic
Acknowledgments
J.W. was supported by ERA-NET NEURON MODDIFSYN. M.D. was supported by grant from Polish Ministry of Science and Higher Education no. N N301 033134. This work was supported by the COST Action BM1001 “Brain Extracellular Matrix in Health and Disease”. We thank Prof L. Kaczmarek and Prof G.M. Wilczynski for valuable discussions and suggestions regarding the manuscripts.
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