Open AccessDistinct functions for the catalytic and hemopexin domains of a Drosophila matrix metalloproteinase
Author(s) -
Bernadette M. Glasheen,
Aashish Kabra,
Andrea Page-McCaw
Publication year - 2009
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0804171106
Subject(s) - hemopexin , matrix metalloproteinase , mmp1 , biology , drosophila melanogaster , phenotype , microbiology and biotechnology , extracellular matrix , genetics , null allele , gene , biochemistry , enzyme , gene expression , heme
Human matrix metalloproteinases (MMPs) are believed to contribute to tumor progression. Therapies based on inhibiting the catalytic domain of MMPs have been unsuccessful, but these studies raise the question of whether other MMP domains might be appropriate targets. The genetic dissection of domain function has been stymied in mouse because there are 24 related and partially redundant MMP genes in the mouse genome. Here, we present a genetic dissection of the functions of the hemopexin and catalytic domains of a canonical MMP inDrosophila melanogaster , an organism with only 2 MMPs that function nonredundantly. We compare the phenotypes ofMmp1 null alleles with alleles that have specific hemopexin domain lesions, and we also examine phenotypes of dominant-negative mutants. We find that, although the catalytic domain appears to be required for all MMP functions including extracellular matrix remodeling of the tracheal system, the hemopexin domain is required specifically for tissue invasion events later in metamorphosis but not for tracheal remodeling. Thus, we find that this MMP hemopexin domain has an apparent specialization for tissue invasion events, a finding with potential implications for inhibitor therapies.