MIG-17/ADAMTS controls cell migration by recruiting nidogen to the basement membrane in C. elegans

Yukihiko Kubota, Kiyotaka Ohkura, Katsuyuki K. Tamai, Kayo Nagata, Kiyoji Nishiwaki

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    Abstract

    Mutations in the a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) family of secreted proteases cause diseases linked to ECM abnormalities. However, the mechanisms by which these enzymes modulate the ECM during development are mostly unexplored. The Caenorhabditis elegans MIG-17/AD-AMTS protein is secreted from body wall muscle cells and localizes to the basement membrane (BM) of the developing gonad where it controls directional migration of gonadal leader cells. Here we show that specific amino acid changes in the ECM proteins fibulin-1C (FBL-1C) and type IV collagen (LET-2) result in bypass of the requirement for MIG-17 activity in gonadal leader cell migration in a nidogen (NID-1)-dependent and -independent manner, respectively. The MIG-17, FBL-1C and LET-2 activities are required for proper accumulation of NID-1 at the gonadal BM. However, mutant FBL-1C or LET-2 in the absence of MIG-17 promotes NID-1 localization. Furthermore, overexpression of NID-1 in mig-17 mutants substantially rescues leader cell migration defects. These results suggest that functional interactions among BM molecules are important for MIG-17 control of gonadal leader cell migration. We propose that FBL-1C and LET-2 act downstream of MIG-17-dependent proteolysis to recruit NID-1 and that LET-2 also activates a NID-1-independent pathway, thereby inducing the remodeling of the BM required for directional control of leader cell migration.

    Original languageEnglish
    Pages (from-to)20804-20809
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume105
    Issue number52
    DOIs
    Publication statusPublished - 2008 Dec 30

    Keywords

    • ECM
    • Fibulin-1
    • Organogenesis
    • Type IV collagen

    ASJC Scopus subject areas

    • General

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