title: A fibulin-1 homolog interacts with an ADAM protease that controls cell migration in C. elegans.
abstract: ADAM (a disintegrin and metalloprotease) family proteins play important roles in animal development and pathogenesis. In C. elegans, a secreted ADAM protein, MIG-17, acts from outside the gonad to control the migration of gonadal distal tip cells (DTCs) that promote gonad morphogenesis. Here, we report that dominant mutations in the fbl-1 gene encoding fibulin-1 spliced isoforms, which are calcium binding extracellular matrix proteins, bypass the requirement for MIG-17 activity in directing DTC migration. Specific amino acid substitutions in the third EGF-like motif of one of the two isoforms, FBL-1C, which corresponds to mammalian fibulin-1C, suppress mig-17 mutations. FBL-1C is synthesized in the gut cells and localizes strongly to the gonadal basement membrane in a MIG-17-dependent manner. Localization of mutant FBL-1C is weaker than that of the wild-type protein and is insensitive to MIG-17 activity, suggesting that it gains a novel function that compensates for its reduced molecular density. We propose that proteolysis by MIG-17 recruits FBL-1C to the gonadal basement membrane, where it is required for the guidance of DTCs, and that mutant FBL-1C acts in a manner that mimics the downstream events of MIG-17-mediated proteolysis.
authors.affiliation: RIKEN Center for Developmental Biology, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Kubota
authors.forename: Rie
authors.initials: R
authors.lastname: Kuroki
authors.forename: Kiyoji
authors.initials: K
authors.lastname: Nishiwaki
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D017931:DNA Primers; D019483:Disintegrins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006066:Gonads / Q000254:growth & development*; D008666:Metalloendopeptidases / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009154:Mutation / Q000235:genetics; D038081:Organogenesis / Q000502:physiology*; D010957:Plasmids / Q000235:genetics; D020033:Protein Isoforms; D015398:Signal Transduction / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D017931:DNA Primers; D019483:Disintegrins; C410348:MIG-17 protein, C elegans; D020033:Protein Isoforms; C060820:fibulin; D008666:Metalloendopeptidases