Prodomain-dependent tissue targeting of an ADAMTS protease controls cell migration in Caenorhabditis elegans.
Members of the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family of secreted proteins play important roles in animal development and pathogenesis. However, the lack of in vivo models has hampered elucidation of the mechanisms by which these enzymes are recruited to specific target tissues and the timing of their activation during development. Using transgenic worms and primary cell cultures, here we show that MIG-17, an ADAMTS family protein required for gonadal leader cell migration in Caenorhabditis elegans, is recruited to the gonadal basement membrane in a prodomain-dependent manner. The activation of MIG-17 to control leader cell migration requires prodomain removal, which is suggested to occur autocatalytically in vitro. Although the prodomains of ADAMTS proteases have been implicated in maintaining enzymatic latency, polypeptide folding and secretion, our findings demonstrate that the prodomain has an unexpected function in tissue-specific targeting of MIG-17; this prodomain targeting function may be shared by other ADAMTSs including those in vertebrates.
Ihara
Shinji
S
RIKEN Center for Developmental Biology, Kobe, Japan.
Nishiwaki
Kiyoji
K
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D001485:Basement Membrane / Q000378:metabolism*; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D019483:Disintegrins / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D006066:Gonads / Q000378:metabolism* / Q000502:physiology; D008666:Metalloendopeptidases / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D019483:Disintegrins; C410348:MIG-17 protein, C elegans; D008666:Metalloendopeptidases