A fibulin-1 homolog interacts with an ADAM protease that controls cell migration in C. elegans

Yukihiko Kubota, Rie Kuroki, Kiyoji Nishiwaki

    Research output: Contribution to journalArticlepeer-review

    51 Citations (Scopus)

    Abstract

    ADAM (a disintegrin and metalloprotease) family proteins play important roles in animal development and pathogenesis [1]. 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 [2]. 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.

    Original languageEnglish
    Pages (from-to)2011-2018
    Number of pages8
    JournalCurrent Biology
    Volume14
    Issue number22
    DOIs
    Publication statusPublished - 2004 Nov 23

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)

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