Nuclear localization of catalytically active MMP-2 in endothelial cells and neurons.

From microscopic organelles and sub-cellular domains to the level of whole tissues, organs, and body parts, living organisms must continuously maintain and renovate structural components. Matrix metalloproteinases (MMPs) comprise a family of over two dozen Zn-dependent endopeptidases thought to be primary effectors of extracellular tissue renewal and remodeling processes. Endogenous inhibitors, particularly the tissue inhibitors of MMPs (TIMPs), counteract MMP-2 proteolytic activity, but also participate in conversion of several pro-MMPs to proteolytically active forms. Numerous pathologies are characterized by imbalances in activities of MMPs relative to TIMPs. MMPs are synthesized and stored in cytoplasmic domains prior to secretion or expression in cell surface-associated form. Several proteases have been identified in cell nuclei, but their functions, regulation, and substrates remain largely unknown. Here we showed that the catalytically active gelatinase MMP-2 is expressed in nuclei of endothelial cells and neurons, but not in glial or Schwannoma cell lines, in a pattern resembling nuclear speckles, and colocalizes with TIMP-1.