title: Dm1-MMP, a matrix metalloproteinase from Drosophila with a potential role in extracellular matrix remodeling during neural development.
abstract: 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 identical to that of most vertebrate MMPs including a signal sequence, a prodomain with the activation locus, a catalytic domain with a zinc-binding site, and a COOH-terminal hemopexin domain. Northern blot analysis of Dm1-MMP expression 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 hybridization experiments demonstrated that Dm1-MMP is expressed in a segmented pattern in cell clusters at the midline during embryonic stage 12-13, when neurons of the central nervous system start to arise. Recombinant Dm1-MMP produced in Escherichia coli exhibits a potent proteolytic activity against 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 extracellular matrix and basement membrane proteins fibronectin and type IV collagen. 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 involved in the extracellular matrix remodeling taking place during the development of the central nervous system in Drosophila.
authors.affiliation: Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Instituto Universitario de Oncologia, Universidad de Oviedo, 33006-Oviedo, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Llano
authors.forename: A M
authors.initials: AM
authors.lastname: Pendás
authors.forename: P
authors.initials: P
authors.lastname: Aza-Blanc
authors.forename: T B
authors.initials: TB
authors.lastname: Kornberg
authors.forename: C
authors.initials: C
authors.lastname: López-Otín
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000201:enzymology; D003001:Cloning, Molecular; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology / Q000201:enzymology* / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D007814:Larva / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D020161:Physical Chromosome Mapping; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D013379:Substrate Specificity; D013876:Thiophenes / Q000494:pharmacology; D019714:Tissue Inhibitor of Metalloproteinases / Q000494:pharmacology
chemical_list: D016326:Extracellular Matrix Proteins; D061965:Matrix Metalloproteinase Inhibitors; D008565:Membrane Proteins; D010455:Peptides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D013876:Thiophenes; D019714:Tissue Inhibitor of Metalloproteinases; D010649:Phenylalanine; C080985:batimastat; C417183:Dm1 matrix metalloproteinase; D020782:Matrix Metalloproteinases