Dm1-MMP, a matrix metalloproteinase from Drosophila with a potential role in extracellular matrix remodeling during neural development

We have cloned and characterized a cDNA encoding Dm1-MMP, the first matrix metalloproteinase (MMP) identified in Drosophila melanogaster. The isolated cDNA encodes a protein of 541 residues that has a domain organization iden tical to that of most vertebrate MMPs including a signal sequence, a prodom ain with the activation locus, a catalytic domain with a zinc-binding site, and a COOH-terminal hemopexin domain, Northern blot analysis of Dm1-MMP ex pression in embryonic and larval adult tissues revealed a strong expression level in the developing embryo at 10-22 h, declining thereafter and being undetectable in adults. Western blot analysis confirmed the presence of pro -and active forms of Dm1-MMP in vivo during larval development. In situ hyb ridization experiments demonstrated that Dm1-MMP is expressed in a segmente d pattern in cell clusters at the midline during embryonic stage 12-13, whe n neurons of the central nervous system start to arise. Recombinant Dm1-MMP produced in Escherichia coli exhibits a potent proteolytic activity agains t synthetic peptides used for analysis of vertebrate MMPs. This activity is inhibited by tissue inhibitors of metalloproteinases and by synthetic MMP inhibitors such as BB-94. Furthermore, Dm1-MMP is able to degrade the extra cellular matrix and basement membrane proteins fibronectin and type TV coll agen. On the basis of these data, together with the predominant expression of Dm1-MMP in embryonic neural cells, we propose that this enzyme may be in volved in the extracellular matrix remodeling taking place during the devel opment of the central nervous system in Drosophila.